Síntesis y cribado de péptidos modificados derivados de lactoferricina bovina como fármacos citotóxicos contra líneas de cáncer de colon
| dc.contributor.advisor | García Castañeda, Javier Eduardo | |
| dc.contributor.author | Cárdenas Martínez, Karen Johanna | |
| dc.contributor.orcid | Cárdenas Martínez, Karen Johanna [0000-0002-7266-8769] | spa |
| dc.date.accessioned | 2024-07-18T16:32:38Z | |
| dc.date.available | 2024-07-18T16:32:38Z | |
| dc.date.issued | 2024-07 | |
| dc.description | Ilustraciones a color, diagramas | spa |
| dc.description.abstract | Research on anticancer peptide drugs has gained interest due to their potency and selectivity. Bovine Lactoferricin (LfcinB) and derived peptides, as used in this study, have shown cytotoxic activity against breast cancer. Therefore, their effect on colon cancer was evaluated, specifically on Caco-2 and HT-29 cell lines, with the latter being more resistant. Two hit peptides, LfcinB (21-25)Pal and 26[F] LfcinB (20-30)2, were identified. Libraries of monomeric and dimeric peptides were constructed from these, resulting in 34 molecules. Their cytotoxic effect was assessed on colon cancer cell lines. This process allowed the identification of key amino acids in the sequence necessary for cytotoxic activity and modifications of interest to enhance it. Fifteen molecules exhibited inhibitory concentrations (IC50) below 200 μg/mL against colon cancer cell lines, with eight considered optimized peptides due to improved activity and selectivity. They remained active in colon cancer cell lines from 2 to 72 hours, showing cytotoxicity in prostate, cervical, and breast cancer lines. Optimized peptides, particularly 3, 19, and LfcinB (21-25)Pal, induced cell death in HT-29 cells primarily through the apoptotic pathway, causing mitochondrial membrane depolarization, caspase overexpression, and morphological changes such as rounding and cell contraction. The toxicity of optimized peptides 3, 19, LfcinB (21-25)Pal, and LfcinB (21-25)Pal2 was evaluated in Galleria mellonella, finding lethal doses (LD50) >100mg/kg. Moreover, peptide 19 toxicity was assessed in CD1 mice through the Irwin test, revealing central nervous system effects with LD50 between 70mg/kg and 140mg/kg. Lastly, the zebrafish model determined the CL50 of this optimized peptide to be between 20-25 μg/mL. It was also found that this optimized peptide exhibited lower in vivo toxicity than the sequence-derived peptide (hit). Based on the results, eight optimized peptides were identified, with peptides 3, 19, and LfcinB (21-25)Pal standing out as candidates for further studies in developing treatments for colon cancer. | eng |
| dc.description.abstract | La investigación en fármacos de origen peptídico anticancerígenos ha ganado interés debido a su potencia y selectividad. La Lactoferricina Bovina (LfcinB) y péptidos derivados, como los utilizados en el presente estudio han mostrado actividad citotóxica frente a cáncer de mama, por lo que se evaluó su efecto sobre cáncer de colon (líneas celulares Caco-2 y HT-29, siendo esta última la más resistente). Se identificaron dos péptidos hit, LfcinB (21-25)Pal y 26[F] LfcinB (20-30)2, a partir de los cuales se construyeron librerías de péptidos monoméricos y diméricos para la obtención de 34 moléculas, cuyo efecto citotóxico se evaluó en líneas celulares de cáncer de colon. Este proceso permitió la identificación de aminoácidos clave de la secuencia que son o no necesarios para la actividad citotóxica y modificaciones de interés para mejorar la actividad. Quince moléculas mostraron concentraciones inhibitorias (IC50) menores de 200 μg/mL frente a las líneas celulares de cáncer de colon, de los cuales ocho fueron considerados como péptidos optimizados por su actividad y selectividad mejorada. Estos fueron activos en líneas celulares de cáncer de colon desde las 2 hasta las 72 horas de tratamiento, algunas también demostraron citotoxicidad en líneas de cáncer de próstata, cuello uterino y mama. Los péptidos optimizados con los mejores resultados 3, 19 y el LfcinB (21-25)Pal indujeron muerte celular en células HT-29 por la vía apoptótica principalmente, causando despolarización de la membrana mitocondrial, sobreexpresión de caspasas y cambios morfológicos como redondeamiento y contracción celular. La toxicidad de los péptidos optimizados 3, 19, LfcinB (21-25)Pal y el LfcinB (21-25)Pal2 fue evaluada en Galleria mellonella, encontrando dosis letales (DL50) >100mg/kg. Por otro lado, la toxicidad del péptido 19 fue evaluada en ratones CD1 mediante la prueba de Irwin, evidenciando que el péptido indujo efectos en el sistema nervioso central y la DL50 está entre 70mg/kg y 140mg/kg. Por último, en el modelo de pez cebra se determinó que la CL50 de este péptido está entre 20-25 μg/mL. Así mismo, se evidenció que este péptido optimizado presentó menor toxicidad in vivo que el péptido del que se derivó su secuencia (péptido hit). A partir de los resultados obtenidos se identificaron ocho péptidos optimizados, de los cuales se destacan los péptidos 3, 19 y LfcinB (21-25)Pal como candidatos para continuar en estudios para el desarrollo de tratamientos contra el cáncer de colon. (Texto tomado de la fuente) | spa |
| dc.description.degreelevel | Doctorado | spa |
| dc.description.degreename | Doctor en Ciencias Farmacéuticas | spa |
| dc.format.extent | 199 páginas | spa |
| dc.format.mimetype | application/pdf | spa |
| dc.identifier.instname | Universidad Nacional de Colombia | spa |
| dc.identifier.reponame | Repositorio Institucional Universidad Nacional de Colombia | spa |
| dc.identifier.repourl | https://repositorio.unal.edu.co/ | spa |
| dc.identifier.uri | https://repositorio.unal.edu.co/handle/unal/86567 | |
| dc.language.iso | spa | spa |
| dc.publisher | Universidad Nacional de Colombia | spa |
| dc.publisher.branch | Universidad Nacional de Colombia - Sede Bogotá | spa |
| dc.publisher.faculty | Facultad de Ciencias | spa |
| dc.publisher.place | Bogotá, Colombia | spa |
| dc.publisher.program | Bogotá - Ciencias - Doctorado en Ciencias Farmacéuticas | spa |
| dc.relation.references | Hanahan, D. & Weinberg, R. A. Hallmarks of Cancer: The Next Generation. Cell, 646–674 (2011). | spa |
| dc.relation.references | Siegel Mph, R. L. et al. Cancer statistics, 2023. CA Cancer J Clin, 17–48 (2023). | spa |
| dc.relation.references | World Health Organization. WHO | Cancer Key statistics. https://www.who.int/cancer/resources/keyfacts/en/ (2020). | spa |
| dc.relation.references | Infografías cáncer en cifras INC - Instituto Nacional de Cancerología. https://www.cancer.gov.co/portafolio-1/salud-publica/grupos/grupo-vigilancia-epidemiologica-del-cancer/infografias-cancer-cifras-inc (2023). | spa |
| dc.relation.references | Bonnor, R. M. & Ludwig, K. A. Laparoscopic colectomy for colon cancer: Comparable to conventional oncologic surgery? Clin Colon Rectal Surg, 174–181 (2005). | spa |
| dc.relation.references | Ministerio de Salud y Protección Social. Guía de Práctica Clínica para la detección temprana, diagnóstico, tratamiento integral, seguimiento y rehabilitación del cáncer de colon y recto. gpc.mimsalud.gov.co (2017). | spa |
| dc.relation.references | Vogel, J. D., et al. The American society of colon and rectal surgeons clinical practice guidelines for the treatment of colon cancer. Dis Colon Rectum, 999–1017 (2017). | spa |
| dc.relation.references | Paschke, S. Value of adjuvant chemotherapy for colon and rectal cancer from a surgeon´s point of view. Practical oncology 1–9 (2017). | spa |
| dc.relation.references | Ramphal, W. et al. Oncologic outcome and recurrence rate following anastomotic leakage after curative resection for colorectal cancer. Surg Oncol, 730–736 (2018). | spa |
| dc.relation.references | Ruiz-tovar, J. et al. De La Cirugía Colónica. Cir Cir, 283–291 (2010). | spa |
| dc.relation.references | Artinyan, A. et al. Infectious postoperative complications decrease long-term survival in patients undergoing curative surgery for colorectal cancer: A study of 12,075 patients. Ann Surg, 497–505 (2015). | spa |
| dc.relation.references | Alves Costa De Jesus, C., et al.. Quality of life of colorectal cancer patients with intestinal stomas Quality of Life of Colorectal Cancer Patients with Intestinal Stomas. J Carcinog Mutagen (2014). | spa |
| dc.relation.references | Hilchie, A. L. et al. Pleurocidin-family cationic antimicrobial peptides are cytolytic for breast carcinoma cells and prevent growth of tumor xenografts. Breast Cancer Research, 1–16 (2011). | spa |
| dc.relation.references | Felício, M. R., et al.. Peptides with dual antimicrobial and anticancer activities. Front Chem, 1–9 (2017). | spa |
| dc.relation.references | Marqus, S., Pirogova, E, Piva, T. J. Evaluation of the use of therapeutic peptides for cancer treatment. J Biomed Sci, (2017). | spa |
| dc.relation.references | Roudi, R., Syn, N. L, Roudbary, M. Antimicrobial peptides as biologic and immunotherapeutic agents against cancer: A comprehensive overview. Frontiers in Immunology (2017). | spa |
| dc.relation.references | Hao, Y. et al. A review of the design and modification of lactoferricins and their derivatives. BioMetals, 331–341 (2018). | spa |
| dc.relation.references | Mader, J. S., Salsman, J., Conrad, D. M, Hoskin, D. W. Bovine lactoferricin selectively induces apoptosis in human leukemia and carcinoma cell lines. Mol Cancer Ther, 612–624 (2005). | spa |
| dc.relation.references | Gibbons, J., Kanwar, R, Kanwar Jagat. Lactoferrin and Cancer in Different Cancer Models. Front Biosci 1080–1088 (2011). | spa |
| dc.relation.references | Insuasty-Cepeda, D. S. et al. Peptides Derived from (RRWQWRMKKLG)2-K-Ahx Induce Selective Cellular Death in Breast Cancer Cell Lines through Apoptotic Pathway. Int J Mol Sci, 4550 (2020). | spa |
| dc.relation.references | Vargas Casanova, Y. et al. Antibacterial Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Cytotoxic Effect against MDA-MB-468 and MDA-MB-231 Breast Cancer Cell Lines. Molecules, 1–11 (2017). | spa |
| dc.relation.references | Barragán-Cárdenas, A. et al. Selective cytotoxic effect against the MDA-MB-468 breast cancer cell line of the antibacterial palindromic peptide derived from bovine lactoferricin. RSC Adv, 17593–17601 (2020). | spa |
| dc.relation.references | Richardson, A., et al.. Intracellular delivery of bovine lactoferricin’s antimicrobial core (RRWQWR) kills T-leukemia cells. Biochem Biophys Res Commun, 736–741 (2009). | spa |
| dc.relation.references | Guerra, J. R. et al. The tetrameric peptide LfcinB (20-25)4 derived from bovine lactoferricin induces apoptosis in the MCF-7 breast cancer cell line. RSC Adv, 20497–20504 (2019). | spa |
| dc.relation.references | Solarte, V. A. et al. A tetrameric peptide derived from bovine lactoferricin as a potential therapeutic tool for oral squamous cell carcinoma: A preclinical model. PLoS One, (2017). | spa |
| dc.relation.references | World Health Organization GLOBOCAN. Cancer Today 2020. https://gco.iarc.fr/today/ (2020). | spa |
| dc.relation.references | Galán, E. F., et al. Manual Para La Detección Temprana Del Cáncer de Colon y Recto. (2015). | spa |
| dc.relation.references | Labianca, R. et al. Colon cancer. Critical Reviews in Oncology/Hematology vol. 74 106–133 (2010). | spa |
| dc.relation.references | Testa, U., Pelosi, E., Castelli, G. Colorectal Cancer: Genetic Abnormalities, Tumor Progression, Tumor Heterogeneity, Clonal Evolution and Tumor-Initiating Cells. Medical Sciences, 31 (2018). | spa |
| dc.relation.references | Fearon, E. R., Vogelstein, B. A genetic model for colorectal tumorigenesis. Cell vol. 61 759–767 (1990). | spa |
| dc.relation.references | Kim, S. H. et al. Tropism between hepatic and pulmonary metastases in colorectal cancers. Oncol Rep, 459–464 (2012). | spa |
| dc.relation.references | Ghidini, M., Petrelli, F, Tomasello, G. Right Versus Left Colon Cancer: Resectable and Metastatic Disease. Current Treatment Options in Oncology (2018). | spa |
| dc.relation.references | Rawla, P., Sunkara, T., Barsouk, A. Epidemiology of colorectal cancer: Incidence, mortality, survival, and risk factors. Przeglad Gastroenterologiczny vol. 14 89–103 (2019). | spa |
| dc.relation.references | Stidham, R. W., Higgins, P. D. R. Colorectal Cancer in Inflammatory Bowel Disease. Clin Colon Rectal Surg, 168–178 (2018). | spa |
| dc.relation.references | Galiano de Sánchez, M. T. Cáncer colorrectal (CCR). Revista Colombia de Gastroenterología, (2005). | spa |
| dc.relation.references | Hamel, J. F. et al. Comparison of treatment to improve gastrointestinal functions after colorectal surgery within enhanced recovery programmes: a systematic review and meta-analysis. Scientific Reports 2021 11:1, 1–12 (2021). | spa |
| dc.relation.references | Banaszkiewicz, Z. et al. Intestinal stoma in patients with colorectal cancer from the perspective of 20-year period of clinical observation. Prz Gastroenterol, 23 (2015). | spa |
| dc.relation.references | Silva, N. M., et al. Psychological aspects of patients with intestinal stoma: integrative review1. Rev Lat Am Enfermagem, 2950 (2017). | spa |
| dc.relation.references | McKenzie, F. et al. Psychological impact of colostomy pouch change and disposal. Br J Nurs, 308–316 (2006). | spa |
| dc.relation.references | Brown, S. R. et al. The Impact of Postoperative Complications on Long-term Quality of Life After Curative Colorectal Cancer Surgery. Ann Surg, 916–923 (2014). | spa |
| dc.relation.references | Alty, I. G. et al. Refusal of surgery for colon cancer: Sociodemographic disparities and survival implications among US patients with resectable disease. The American Journal of Surgery, 39–45 (2021). | spa |
| dc.relation.references | Benson, A. B. et al. NCCN Guidelines Version 2.2021 Colon Cancer NCCN Framework TM : Basic Resources Continue NCCN Guidelines Panel Disclosures. (2021). | spa |
| dc.relation.references | Aparicio, T. Oxaliplatin, fluorouracil and leucovorin as adjuvant treatment for colon cancer. Colon and Rectum, 33–35 (2011). | spa |
| dc.relation.references | Yamazaki, K. et al. Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G). Annals of Oncology, 1539–1546 (2016). | spa |
| dc.relation.references | Longley, D. B., Harkin, D. P. & Johnston, P. G. 5-Fluorouracil: mechanisms of action and clinical strategies. Nature Reviews Cancer, 330–338 (2003). | spa |
| dc.relation.references | Walko, C. M. & Lindley, C. Capecitabine: A review. Clin Ther, 23–44 (2005). | spa |
| dc.relation.references | Alcindor, T. & Beauger, N. Oxaliplatin: a review in the era of molecularly targeted therapy. Current Oncology, 18 (2011). | spa |
| dc.relation.references | Kciuk, M., Marciniak, B., Kontek, R. Irinotecan—Still an Important Player in Cancer Chemotherapy: A Comprehensive Overview. International Journal of Molecular Sciences, 4919 (2020). | spa |
| dc.relation.references | De Rosa, M. et al. The biological complexity of colorectal cancer: Insights into biomarkers for early detection and personalized care. Therapeutic Advances in Gastroenterology, 861–886 (2016). | spa |
| dc.relation.references | Kazazi-Hyseni, F., Beijnen, J. H. & Schellens, J. H. M. Bevacizumab. Oncologist, 819 (2010). | spa |
| dc.relation.references | Kronfol, M. M. & McClay, J. L. Epigenetic biomarkers in personalized medicine. Prognostic Epigenetics 375–395 (2019). | spa |
| dc.relation.references | Nguyen, C. M. & Jacob, S. E. Pembrolizumab. J Dermatol Nurses Assoc, 95–97 (2017). | spa |
| dc.relation.references | Carrera, P. M., Kantarjian, H. M. & Blinder, V. S. The financial burden and distress of patients with cancer: Understanding and stepping-up action on the financial toxicity of cancer treatment. CA Cancer J Clin, 153–165 (2018). | spa |
| dc.relation.references | Siddiqui, M. & Rajkumar, S. V. The High Cost of Cancer Drugs and What We Can Do About It. JMCP, 935–943 (2012). | spa |
| dc.relation.references | Kunnumakkara, A. B. et al. Cancer drug development: The missing links. Experimental Biology and Medicine, 663–689 (2019). | spa |
| dc.relation.references | Ronen, J., Hayat, S. & Akalin, A. Methods Evaluation of colorectal cancer subtypes and cell lines using deep learning (2019). | spa |
| dc.relation.references | Menter, D. G. et al. Back to the Colorectal Cancer Consensus Molecular Subtype Future. Curr Gastroenterol Rep, 5 (2019). | spa |
| dc.relation.references | Guinney, J. et al. The consensus molecular subtypes of colorectal cancer. Nat Med, 1350–1356 (2015). | spa |
| dc.relation.references | Okita, A. et al. Consensus molecular subtypes classification of colorectal cancer as a predictive factor for chemotherapeutic efficacy against metastatic colorectal cancer. Oncotarget, 18698 (2018). | spa |
| dc.relation.references | Baker, S. et al. Cancer Hallmarks Analytics Tool (CHAT): A text mining approach to organize and evaluate scientific literature on cancer. Bioinformatics, 3973–3981 (2017). | spa |
| dc.relation.references | Paul, D. The systemic hallmarks of cancer. J Cancer Metastasis Treat, (2020). | spa |
| dc.relation.references | Alves, A. C., Ribeiro, D., Nunes, C. & Reis, S. Biophysics in cancer: The relevance of drug-membrane interaction studies. Biochimica et Biophysica Acta – Biomembranes, 2231–2244 (2016). | spa |
| dc.relation.references | Sherbet, G. V. Membrane Fluidity and Cancer Metastasis. Pathobiology, 198–205 (1989). | spa |
| dc.relation.references | Chiangjong, W., Chutipongtanate, S. & Hongeng, S. Anticancer peptide: Physicochemical property, functional aspect and trend in clinical application (Review). International Journal of Oncology vol, 678–696 (2020). | spa |
| dc.relation.references | Bhatia, R. et al. Cancer-associated mucins: role in immune modulation and metastasis. Cancer and Metastasis Reviews, 223–236 (2019). | spa |
| dc.relation.references | Ren, J. et al. Correlation between the Presence of Microvilli and the Growth or Metastatic Potential of Tumor Cells. Japanese Journal of Cancer Research, 920–926 (1990). | spa |
| dc.relation.references | Butler, L. M. et al. Lipids and cancer: Emerging roles in pathogenesis, diagnosis and therapeutic intervention. Advanced Drug Delivery Reviews, 245–293 (2020). | spa |
| dc.relation.references | Yang, M. & Brackenbury, W. J. Membrane potential and cancer progression. Frontiers in Physiology (2013). | spa |
| dc.relation.references | Baba, A. I. & Câtoi, C. Tumor cell morphology. (2007). | spa |
| dc.relation.references | Fischer, E. G. Nuclear Morphology and the Biology of Cancer Cells. Acta Cytol, 511–519 (2020). | spa |
| dc.relation.references | Thiran, J. P., Macq, B., Mairesse, J. Morphological classification of cancerous cells. Proceedings - International Conference on Image Processing, 706–710 (1994). | spa |
| dc.relation.references | Hilchie, A. L., Hoskin, D. W, Power Coombs, M. R. Anticancer activities of natural and synthetic peptides. in Advances in Experimental Medicine and Biology, 131–147 (2019). | spa |
| dc.relation.references | Xie, M., Liu, D., Yang, Y. Anti-cancer peptides: Classification, mechanism of action, reconstruction and modification: Anticancer peptides. Open Biology (2020). | spa |
| dc.relation.references | Qin, Y. et al. From Antimicrobial to Anticancer Peptides: The Transformation of Peptides. Recent Pat Anticancer Drug Discov, 70–84 (2019). | spa |
| dc.relation.references | Camilio, K. A., Rekdal, Ø., Sveinbjörnsson, B. LTX-315 (OncoporeTM): A short synthetic anticancer peptide and novel immunotherapeutic agent. Oncoimmunology, (2014). | spa |
| dc.relation.references | Stangelberger, A., Schally, A. V., Djavan, B. New Treatment Approaches for Prostate Cancer Based on Peptide Analogues. European Urology, 890–900 (2008). | spa |
| dc.relation.references | Garton, M. et al. Method to generate highly stable D-amino acid analogs of bioactive helical peptides using a mirror image of the entire PDB. Proc Natl Acad Sci U S A, 1505–1510 (2018). | spa |
| dc.relation.references | Gentilucci, L., De Marco, R., Cerisoli, L. Chemical Modifications Designed to Improve Peptide Stability: Incorporation of Non-Natural Amino Acids, Pseudo-Peptide Bonds, and Cyclization. Curr Pharm Des, 3185–3203 (2010). | spa |
| dc.relation.references | Vlieghe, P., Lisowski, V., Martinez, J., Khrestchatisky, M. Synthetic therapeutic peptides: science and market. Drug Discovery Today vol. 15 40–56 (2010). | spa |
| dc.relation.references | Otvos, L. & Wade, J. D. Current challenges in peptide-based drug discovery. Front Chem (2014). | spa |
| dc.relation.references | D’Arcy, M. S. Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int, 582–592 (2019). | spa |
| dc.relation.references | Sancho-Martínez, S. M et al. Necrotic Concentrations of Cisplatin Activate the Apoptotic Machinery but Inhibit Effector Caspases and Interfere with the Execution of Apoptosis. Toxicological Sciences, 73–85 (2011). | spa |
| dc.relation.references | Johnstone, R. W., Ruefli, A. A., Lowe, S. W. Apoptosis: A Link between Cancer Genetics and Chemotherapy. Cell, 153–164 (2002). | spa |
| dc.relation.references | Hoskin, D. W. & Ramamoorthy, A. Studies on anticancer activities of antimicrobial peptides. Biochim Biophys Acta Biomembr, 357–375 (2008). | spa |
| dc.relation.references | Papo, N. & Shai, Y. Host defense peptides as new weapons in cancer treatment. Cellular and Molecular Life Sciences CMLS, 784–790 (2005). | spa |
| dc.relation.references | Zhou, X. R. et al. From a pro-apoptotic peptide to a lytic peptide: One single residue mutation. Biochimica et Biophysica Acta (BBA) - Biomembranes, 1914–1925 (2016). | spa |
| dc.relation.references | Arias, M. et al. Selective anticancer activity of synthetic peptides derived from the host defence peptide tritrpticin. Biochim Biophys Acta Biomembr, (2020). | spa |
| dc.relation.references | Kashyap, D., Garg, V. K., Goel, N. Intrinsic and extrinsic pathways of apoptosis: Role in cancer development and prognosis. Adv Protein Chem Struct Biol, 73–120 (2021). | spa |
| dc.relation.references | Min, K. A., Maharjan, P., Ham, S., Shin, M. C. Pro-apoptotic peptides-based cancer therapies: challenges and strategies to enhance therapeutic efficacy. Arch Pharm Res, 594–616 (2018). | spa |
| dc.relation.references | Faraji, N., Arab, S. S., Doustmohammadi, A., Daly, N. L., Khosroushahi, A. Y. ApInAPDB: a database of apoptosis-inducing anticancer peptides. Scientific Reports 2022, 1–7 (2022). | spa |
| dc.relation.references | Wang, H. et al. Antimicrobial Peptides Mediate Apoptosis by Changing Mitochondrial Membrane Permeability. Int J Mol Sci, (2022). | spa |
| dc.relation.references | Zong, W. X. & Thompson, C. B. Necrotic death as a cell fate. Genes Dev, 1–15 (2006). | spa |
| dc.relation.references | Kim, J. J. Y. et al. Necrosis-inducing peptide has the beneficial effect on killing tumor cells through neuropilin (NRP-1) targeting. Oncotarget, 32449 (2016). | spa |
| dc.relation.references | Lu, Y. et al. PFR peptide, one of the antimicrobial peptides identified from the derivatives of lactoferrin, induces necrosis in leukemia cells. Scientific Reports 2016, 1–12 (2016). | spa |
| dc.relation.references | Do, T. N. et al. Preferential induction of necrosis in human breast cancer cells by a p53 peptide derived from the MDM2 binding site. Oncogene 2003, 1431–1444 (2003). | spa |
| dc.relation.references | Qiu, Y. et al. Cell-penetrating peptides induce apoptosis and necrosis through specific mechanism and cause impairment of Na+–K+-ATPase and mitochondria. Amino Acids, 75–88 (2017). | spa |
| dc.relation.references | Decraene, B. et al. Immunogenic cell death and its therapeutic or prognostic potential in high-grade glioma. Genes & Immunity, 1–11 (2022). | spa |
| dc.relation.references | Zhou, J. et al. Immunogenic cell death in cancer therapy: Present and emerging inducers. J Cell Mol Med, 4854 (2019). | spa |
| dc.relation.references | Aria, H., Rezaei, M. Immunogenic cell death inducer peptides: A new approach for cancer therapy, current status and future perspectives. Biomedicine & Pharmacotherapy, 114503 (2023). | spa |
| dc.relation.references | Mathew, R., Karantza-Wadsworth, V. , White, E. Role of autophagy in cancer. Nature Reviews Cancer, 961–967 (2007). | spa |
| dc.relation.references | Tilija Pun, N., Jang, W. J. & Jeong, C. H. Role of autophagy in regulation of cancer cell death/apoptosis during anti-cancer therapy: focus on autophagy flux blockade. Arch Pharm Res, 475–488 (2020). | spa |
| dc.relation.references | Thorburn, A., Thamm, D. H. & Gustafson, D. L. Autophagy and Cancer Therapy. Mol Pharmacol, 830 (2014). | spa |
| dc.relation.references | Ren, S. X. et al. FK-16 Derived from the Anticancer Peptide LL-37 Induces Caspase-Independent Apoptosis and Autophagic Cell Death in Colon Cancer Cells. PLoS One (2013). | spa |
| dc.relation.references | Shoji-Kawata, S. et al. Identification of a candidate therapeutic autophagy-inducing peptide. Nature, 201–206 (2013). | spa |
| dc.relation.references | Pan, W. R. et al. Bovine lactoferricin B induces apoptosis of human gastric cancer cell line AGS by inhibition of autophagy at a late stage. J Dairy Sci, 7511–7520 (2013). | spa |
| dc.relation.references | Tomita, M. et al. Twenty-five years of research on bovine lactoferrin applications. Biochimie, 52–57 (2009). | spa |
| dc.relation.references | Cutone, A. et al. Lactoferrin’s anti-cancer properties: Safety, selectivity, and wide range of action. Biomolecules vol. 10, (2020). | spa |
| dc.relation.references | Tsuda, H., Sekine, K., Fujita, K. I., Iigo, M. Cancer prevention by bovine lactoferrin and underlying mechanisms - A review of experimental and clinical studies. in Biochemistry and Cell Biology, 131–136 (2002). | spa |
| dc.relation.references | Iigo, M. et al. Inhibition of intestinal polyp growth by oral ingestion of bovine lactoferrin and immune cells in the large intestine. BioMetals, 1017–1029 (2014). | spa |
| dc.relation.references | Cutone, A. et al. Lactoferrin in the Prevention and Treatment of Intestinal Inflammatory Pathologies Associated with Colorectal Cancer Development. Cancers (Basel), 3806 (2020). | spa |
| dc.relation.references | Tanaka, H. et al. Effects of oral bovine lactoferrin on a mouse model of inflammation associated colon cancer. Biochemistry and Cell Biology, 1–7 (2020). | spa |
| dc.relation.references | Giansanti, F., Panella, G., Leboffe, L., Antonini, G. Lactoferrin from Milk: Nutraceutical and Pharmacological Properties. Pharmaceuticals, 61 (2016). | spa |
| dc.relation.references | Arias, M. et al. Anticancer activities of bovine and human lactoferricin-derived peptides1. in Biochemistry and Cell Biology, 91–98 (2017). | spa |
| dc.relation.references | Sadiq, I. Z., Babagana, K., Danlami, D., Abdullahi, L. I., Khan, A. R. Molecular Therapeutic Cancer Peptides: A Closer Look at Bovine Lactoferricin. Asian Journal of Biochemistry, Genetics and Molecular Biology, 1–9 (2018). | spa |
| dc.relation.references | Zhou, N., Tieleman, D. P., Vogel, H. J. Molecular dynamics simulations of bovine lactoferricin: turning a helix into a sheet. Biometals, 217–223 (2004). | spa |
| dc.relation.references | Huertas, N., et al. Antimicrobial Activity of Truncated and Polyvalent Peptides Derived from the FKCRRQWQWRMKKGLA Sequence against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923. Molecules, 987 (2017). | spa |
| dc.relation.references | Tolokh, I. S., et al.. Binding free energy and counterion release for adsorption of the antimicrobial peptide lactoferricin B on a POPG membrane. Phys Rev E Stat Nonlin Soft Matter Phys, (2009). | spa |
| dc.relation.references | Rahman, R. et al. Inhibition of breast cancer xenografts in a mouse model and the induction of apoptosis in multiple breast cancer cell lines by lactoferricin B peptide. J Cell Mol Med, 7181–7189 (2021). | spa |
| dc.relation.references | Furlong, S. J., Mader, J. S., Hoskin, D. W. Lactoferricin-induced apoptosis in estrogen-nonresponsive MDA-MB-435 breast cancer cells is enhanced by C6 ceramide or tamoxifen. Oncol Rep, 1385–1390 (2006). | spa |
| dc.relation.references | Muj, C., Mukhopadhyay, S., Jana, P., Kondapi, A. K. Synergistic action of lactoferrin in enhancing the safety and effectiveness of docetaxel treatment against prostate cancer. Cancer Chemother Pharmacol, 375–387 (2023). | spa |
| dc.relation.references | Guedes, J. P., Pereira, C. S., Rodrigues, L. R., Côrte-Real, M. Bovine milk lactoferrin selectively kills highly metastatic prostate cancer PC-3 and osteosarcoma MG-63 cells in vitro. Front Oncol, 355424 (2018). | spa |
| dc.relation.references | Tone Eliassen, L. et al. Evidence for a direct antitumor mechanism of action of bovine lactoferricin. Anticancer Res, 2703–2710 (2002). | spa |
| dc.relation.references | Mistry, N. et al. The anti-papillomavirus activity of human and bovine lactoferricin. Antiviral Res, 258–265 (2007). | spa |
| dc.relation.references | Jiang, R. & Lönnerdal, B. Bovine lactoferrin and lactoferricin exert antitumor activities on human colorectal cancer cells (HT-29) by activating various signaling pathways1. in Biochemistry and Cell Biology, 99–109 (2017). | spa |
| dc.relation.references | Freiburghaus, C., Janicke, B., Lindmark-Månsson, H., Oredsson, S. M. & Paulsson, M. A. Lactoferricin treatment decreases the rate of cell proliferation of a human colon cancer cell line. J Dairy Sci, 2477–2484 (2009). | spa |
| dc.relation.references | Freiburghaus, C., Lindmark-Månsson, H., Paulsson, M. & Oredsson, S. Reduction of ultraviolet light-induced DNA damage in human colon cancer cells treated with a lactoferrin-derived peptide. J Dairy Sci, 5552–5560 (2012). | spa |
| dc.relation.references | Spicer, J. et al. Safety, anti-tumor activity and T-cell responses in a dose-ranging phase 1 trial of the oncolytic peptide LTX-315 in patients with solid tumors. Clinical Cancer Research, 3435 (2021). | spa |
| dc.relation.references | Tomita, M., Wakabayashi, H., Yamauchi, K., Teraguchi, S., Hayasawa, H. Bovine lactoferrin and lactoferricin derived from milk: Production and applications. in Biochemistry and Cell Biology, 109–112 (2002). | spa |
| dc.relation.references | Agouridas, V. et al. Native Chemical Ligation and Extended Methods: Mechanisms, Catalysis, Scope, and Limitations. Chemical Reviews (2019). | spa |
| dc.relation.references | Jensen, K. J. Solid-phase peptide synthesis: An introduction. Methods in Molecular Biology, 1–21 (2013). | spa |
| dc.relation.references | Kato, H., Hayashi, M., Fukumori, Y., Kaneko, H. MHC restriction in contact hypersensitivity to dicyclohexylcarbodiimide. Food and Chemical Toxicology, 1713–1718 (2002). | spa |
| dc.relation.references | Graham, J. C. et al. An Evaluation of the Occupational Health Hazards of Peptide Couplers. Chem Res Toxicol, 1011–1022 (2022). | spa |
| dc.relation.references | Navarrete, E. L. Síntesis de péptidos. Universidad nacional autonoma de méxico, Instituto de Biotecnología, 1–53 (2007). | spa |
| dc.relation.references | Manne, S. R. et al. Understanding OxymaPure as a Peptide Coupling Additive: A Guide to New Oxyma Derivatives. ACS Omega, 6007–6023 (2022). | spa |
| dc.relation.references | Román Bothia, J. T. Implementación y optimización del proceso sintético de i) complejos aminoácido - estaño IV y ii) péptidos conjugados con Ferroceno, como contribución al desarrollo de fármacos basados en moléculas Organometálicas. (Universidad Nacional de Colombia, Bogotá, 2020). | spa |
| dc.relation.references | Vrettos, E. I. et al. Unveiling and tackling guanidinium peptide coupling reagent side reactions towards the development of peptide-drug conjugates. RSC Adv, 50519–50526 (2017). | spa |
| dc.relation.references | Luna, O. F. et al. Deprotection Reagents in Fmoc Solid Phase Peptide Synthesis: Moving Away from Piperidine? Molecules, (2016). | spa |
| dc.relation.references | Fields, G. B. Methods for Removing the Fmoc Group. Peptide Synthesis Protocols 17–27 (1994). | spa |
| dc.relation.references | Suzuki, R. & Konno, H. Stain Protocol for the Detection of N-Terminal Amino Groups during Solid-Phase Peptide Synthesis. ACS Appl Mater Interfaces (2020). | spa |
| dc.relation.references | Yemm, E. W., Cocking, E. C., Ricketts, R. E. The determination of amino-acids with ninhydrin. Analyst, 209–214 (1955). | spa |
| dc.relation.references | Pedersen, S. L., Jensen, K. J. Peptide release, side-chain deprotection, work-up, and isolation. Methods Mol Biol, 43–63 (2013). | spa |
| dc.relation.references | Craik, D. J. & Kan, M. W. How can we improve peptide drug discovery? Learning from the past, 1399–1402 (2021). | spa |
| dc.relation.references | Muttenthaler, M., King, G. F., Adams, D. J. & Alewood, P. F. Trends in peptide drug discovery. Nature Reviews Drug Discovery, 309–325 (2021). | spa |
| dc.relation.references | Henninot, A., Collins, J. C. & Nuss, J. M. The Current State of Peptide Drug Discovery: Back to the Future? Journal of Medicinal Chemistry vol. 61, 1382–1414 (2018). | spa |
| dc.relation.references | Timur, S. S. & Gürsoy, R. N. The role of peptide-based therapeutics in oncotherapy. J Drug Target, 1048–1062 (2021). | spa |
| dc.relation.references | McErlean, E. M. et al. Rational design and characterisation of a linear cell penetrating peptide for non-viral gene delivery. Journal of Controlled Release, 1288–1299 (2021). | spa |
| dc.relation.references | Pappa, E. V. et al. Structure–activity studies of lGnRH-III through rational amino acid substitution and NMR conformational studies. Peptide Science, 525–534 (2012). | spa |
| dc.relation.references | Kumar, A. et al. Single Amino Acid Substitutions at Specific Positions of the Heptad Repeat Sequence of Piscidin-1 Yielded Novel Analogs That Show Low Cytotoxicity and In Vitro and In Vivo Antiendotoxin Activity. Antimicrob Agents Chemother, 3687 (2016). | spa |
| dc.relation.references | Irazazabal, L. N. et al. Selective amino acid substitution reduces cytotoxicity of the antimicrobial peptide mastoparan. Biochimica et Biophysica Acta (BBA) - Biomembranes, 2699–2708 (2016). | spa |
| dc.relation.references | Schmidt, S. et al. Identification of Short Hydrophobic Cell-Penetrating Peptides for Cytosolic Peptide Delivery by Rational Design. Bioconjug Chem, 382–389 (2017). | spa |
| dc.relation.references | Räder, A. F. B. et al. Orally Active Peptides: Is There a Magic Bullet? Angewandte Chemie International Edition, 14414–14438 (2018). | spa |
| dc.relation.references | Hicks, R. P. Antibacterial and anticancer activity of a series of novel peptides incorporating cyclic tetra-substituted C(α) amino acids. Bioorg Med Chem, 4056–4065 (2016). | spa |
| dc.relation.references | Scorciapino, M. A., Serra, I., Manzo, G. & Rinaldi, A. C. Antimicrobial dendrimeric peptides: Structure, activity and new therapeutic applications. Int J Mol Sci, (2017). | spa |
| dc.relation.references | Liu, S. P., Zhou, L., Lakshminarayanan, R. & Beuerman, R. W. Multivalent antimicrobial peptides as therapeutics: Design principles and structural diversities. in International Journal of Peptide Research and Therapeutics, 199–213 (2010). | spa |
| dc.relation.references | Lorenzon, E. N., Piccoli, J. P., Santos-Filho, N. A. & Cilli, E. M. Dimerization of Antimicrobial Peptides: A Promising Strategy to Enhance Antimicrobial Peptide Activity. Protein Pept Lett, 98–107 (2019). | spa |
| dc.relation.references | Zhong, J. & Chau, Y. Synthesis, characterization, and thermodynamic study of a polyvalent lytic peptide-polymer conjugate as novel anticancer agent. Bioconjug Chem, 2055–2064 (2010). | spa |
| dc.relation.references | Gunasekera, S., Muhammad, T., Strömstedt, A. A., Rosengren, K. J. & Göransson, U. Backbone Cyclization and Dimerization of LL-37-Derived Peptides Enhance Antimicrobial Activity and Proteolytic Stability. Front Microbiol, 1–15 (2020). | spa |
| dc.relation.references | Tam, J. P. & Zavala, F. Multiple antigen peptide. A novel approach to increase detection sensitivity of synthetic peptides in solid-phase immunoassays. J Immunol Methods, 53–61 (1989). | spa |
| dc.relation.references | Bondaryk, M., Staniszewska, M., Zielińska, P. & Urbańczyk-Lipkowska, Z. Natural antimicrobial peptides as inspiration for design of a new generation antifungal compounds. Journal of Fungi (2017). | spa |
| dc.relation.references | Galati, R., Verdina, A., Falasca, G. & Chersi, A. Increased resistance of peptides to serum proteases by modification of their amino groups. Zeitschrift fur Naturforschung - Section C Journal of Biosciences, 558–561 (2003). | spa |
| dc.relation.references | Arispe, N., Carlos Diaz, J. & Flora, M. Efficiency of Histidine-Associating Compounds for Blocking the Alzheimer’s Ab Channel Activity and Cytotoxicity. Biophys J, (2008). | spa |
| dc.relation.references | Feng, Z. & Xu, B. Inspiration from the mirror: D-amino acid containing peptides in biomedical approaches. Biomolecular Concepts, 179–187 (2016). | spa |
| dc.relation.references | Oliva, R. et al. Exploring the role of unnatural amino acids in antimicrobial peptides. Sci Rep, 8888 (2018). | spa |
| dc.relation.references | Cardoso, M. H., Cândido, E. S., Oshiro, K. G. N., Rezende, S. B. & Franco, O. L. Peptides containing D-amino acids and retro-inverso peptides: General applications and special focus on antimicrobial peptides. in Peptide Applications in Biomedicine, Biotechnology and Bioengineering, 131–155 (2018). | spa |
| dc.relation.references | Aghamiri, S. et al. Antimicrobial peptides as potential therapeutics for breast cancer. Pharmacol Res, 105777 (2021). | spa |
| dc.relation.references | Gan, B. H., Gaynord, J., Rowe, S. M., Deingruber, T., Spring, D. R. The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions. Chem Soc Rev, 7820–7880 (2021). | spa |
| dc.relation.references | Kowalczyk, R., Harris, P. W. R., Williams, G. M., Yang, S. H. & Brimble, M. A. Peptide lipidation - A synthetic strategy to afford peptide based therapeutics. Advances in Experimental Medicine and Biology, 185–227 (2017). | spa |
| dc.relation.references | Albada, B. Tuning Activity of Antimicrobial Peptides by Lipidation. Health Consequences of Microbial Interactions with Hydrocarbons, Oils, and Lipids, 317–334 (2018). | spa |
| dc.relation.references | Morstein, J. et al. Medium-Chain Lipid Conjugation Facilitates Cell-Permeability and Bioactivity. J Am Chem Soc, 18532–18544 (2022). | spa |
| dc.relation.references | Wang, D. et al. Anticancer Properties of Lipidated Peptide Drug Supramolecular Self-Assemblies with Enhanced Stability. ACS Appl Bio Mater, 5995–6003 (2019). | spa |
| dc.relation.references | Menacho-Melgar, R., Decker, J. S., Hennigan, J. N. & Lynch, M. D. A review of lipidation in the development of advanced protein and peptide therapeutics. Journal of Controlled Release, 1–12 (2019). | spa |
| dc.relation.references | Wang, Y. et al. The molecular basis for the prolonged blood circulation of lipidated incretin peptides: Peptide oligomerization or binding to serum albumin? J Control Release, 25–33 (2016). | spa |
| dc.relation.references | Zhang, X. et al. A Lipidated Peptide with Mitochondrial Membrane Localization in Human A549 Lung Cells: From Enhanced Cell-Penetrating Properties to Biological Activity Mechanism. ACS Appl Bio Mater, 8277–8290 (2021). | spa |
| dc.relation.references | Bech, E. M., Pedersen, S. L. & Jensen, K. J. Chemical Strategies for Half-Life Extension of Biopharmaceuticals: Lipidation and Its Alternatives. ACS Med Chem Lett, 577–580 (2018). | spa |
| dc.relation.references | Milton Harris, J. & Chess, R. B. Effect of pegylation on pharmaceuticals. Nature Reviews Drug Discovery, 214–221 (2003). | spa |
| dc.relation.references | Porfiryeva, N. N., Moustafine, R. I. & Khutoryanskiy, V. V. PEGylated Systems in Pharmaceutics. Polymer Science - Series C, 62–74 (2020). | spa |
| dc.relation.references | Maiti, S. & Paira, P. Biotin conjugated organic molecules and proteins for cancer therapy: A review. European Journal of Medicinal Chemistry, 206–223 (2018). | spa |
| dc.relation.references | Zempleni, J., Hassan, Y. I. & Wijeratne, S. S. K. Biotin and biotinidase deficiency. Expert Rev Endocrinol Metab, 715–724 (2008). | spa |
| dc.relation.references | Yang, W., Cheng, Y., Xu, T., Wang, X. & Wen, L. ping. Targeting cancer cells with biotin-dendrimer conjugates. Eur J Med Chem, 862–868 (2009). | spa |
| dc.relation.references | Lee, H. S. et al. Mechanism of anticancer activity of buforin IIb, a histone H2A-derived peptide. Cancer Lett, 47–55 (2008). | spa |
| dc.relation.references | Ren, W. X. et al. Recent development of biotin conjugation in biological imaging, sensing, and target delivery. Chemical Communications, 10403–10418 (2015). | spa |
| dc.relation.references | Eliassen, L. T., Haug, B. E., Berge, G. & Rekdal, Ø. Enhanced antitumour activity of 15-residue bovine lactoferricin derivatives containing bulky aromatic amino acids and lipophilic N-terminal modifications. J Pept Sci, 510–517 (2003). | spa |
| dc.relation.references | Svendsen, J. S. M., Grant, T. M., Rennison, D., Brimble, M. A. & Svenson, J. Very Short and Stable Lactoferricin-Derived Antimicrobial Peptides: Design Principles and Potential Uses. Acc Chem Res, 749–759 (2019). | spa |
| dc.relation.references | Vogel, H. J. et al. Towards a structure-function analysis of bovine lactoferricin and related tryptophan- and arginine-containing peptides, 49–63 (2011). | spa |
| dc.relation.references | Arias, M., Piga, K. B., Hyndman, M. E. & Vogel, H. J. Improving the activity of trp-rich antimicrobial peptides by Arg/Lys substitutions and changing the length of cationic residues. Biomolecules (2018). | spa |
| dc.relation.references | Madorran, E., Stožer, A., Bevc, S. & Maver, U. In vitro toxicity model: Upgrades to bridge the gap between preclinical and clinical research. Bosn J Basic Med Sci, 157 (2020). | spa |
| dc.relation.references | Van Norman, G. A. Limitations of Animal Studies for Predicting Toxicity in Clinical Trials: Part 2: Potential Alternatives to the Use of Animals in Preclinical Trials. JACC Basic Transl Sci, 387 (2020). | spa |
| dc.relation.references | HT-29 - HTB-38 | ATCC. https://www.atcc.org/products/htb-38. | spa |
| dc.relation.references | Kleiveland, C. et al. The Impact of Food Bioactives on Health In Vitro and Ex Vivo Models. Chapter 11; HT29 Cell line. | spa |
| dc.relation.references | Caco-2 [Caco2] - HTB-37 | ATCC. https://www.atcc.org/products/htb-37. | spa |
| dc.relation.references | Kleiveland, C. et al. The Impact of Food Bioactives on Health In Vitro and Ex Vivo Models.Chapter 10: Caco-2 Cell line. | spa |
| dc.relation.references | HCT 116 - CCL-247 | ATCC. https://www.atcc.org/products/ccl-247. | spa |
| dc.relation.references | HEK-293 - CRL-1573 | ATCC. https://www.atcc.org/products/crl-1573. | spa |
| dc.relation.references | Thomas, P. & Smart, T. G. HEK293 cell line: A vehicle for the expression of recombinant proteins. J Pharmacol Toxicol Methods, 187–200 (2005). | spa |
| dc.relation.references | DU 145 - HTB-81 | ATCC. https://www.atcc.org/products/htb-81. | spa |
| dc.relation.references | Stone, K. R., Mickey, D. D., Wunderli, H., Mickey, G. H. & Paulson, D. F. Isolation of a human prostate carcinoma cell line (DU 145). Int J Cancer, 274–281 (1978). | spa |
| dc.relation.references | HeLa - CCL-2 | ATCC. https://www.atcc.org/products/ccl-2. | spa |
| dc.relation.references | Horwitz, K. B., Costlow, M. E. & McGuire, W. L. MCF-7: A human breast cancer cell line with estrogen, androgen, progesterone, and glucocorticoid receptors. Steroids, 785–795 (1975). | spa |
| dc.relation.references | MCF7 - HTB-22 | ATCC. https://www.atcc.org/products/htb-22. | spa |
| dc.relation.references | Vargas-Casanova, Y. et al. Synergistic bactericide and antibiotic effects of dimeric, tetrameric, or palindromic peptides containing the RWQWR motif against Gram-positive and Gram-negative strains. RSC Adv, 7239–7245 (2019). | spa |
| dc.relation.references | Barragán‐Cárdenas, A. et al. The Nonapeptide RWQWRWQWR: A Promising Molecule for Breast Cancer Therapy. ChemistrySelect, 9691–9700 (2020). | spa |
| dc.relation.references | Rodríguez, J. Evaluación de la actividad anticancerígena In Vitro de péptidos sintéticos derivados de Lactoferricina Bovina en líneas celulares de cáncer de mama. (Universidad Nacional de Colombia, 2019). | spa |
| dc.relation.references | Ngoma, T. World Health Organization cancer priorities in developing countries. Cancer Initiatives in Developing Countries (2005). | spa |
| dc.relation.references | Magalhaes, L. G., Ferreira, L. L. G. & Andricopulo, A. D. Recent Advances and Perspectives in Cancer Drug Design. An Acad Bras Cienc, 1233–1250 (2018). | spa |
| dc.relation.references | Bray, F. et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 394–424 (2018). | spa |
| dc.relation.references | Orangio, G. R. The Economics of Colon Cancer. Surgical Oncology Clinics of North America, 327–347 (2018). | spa |
| dc.relation.references | Riedl, S., Zweytick, D., Lohner, K. Membrane-active host defense peptides--challenges and perspectives for the development of novel anticancer drugs. Chem Phys Lipids, 766–781 (2011). | spa |
| dc.relation.references | Muller, P. Y. & Milton, M. N. The determination and interpretation of the therapeutic index in drug development. Nat Rev Drug Discov, 751–761 (2012). | spa |
| dc.relation.references | Insuasty Cepeda, D. S. et al. Synthetic Peptide Purification via Solid-Phase Extraction with Gradient Elution: A Simple, Economical, Fast, and Efficient Methodology. Molecules, (2019). | spa |
| dc.relation.references | Busquet, F. et al. OECD validation study to assess intra- and inter-laboratory reproducibility of the zebrafish embryo toxicity test for acute aquatic toxicity testing. Regulatory Toxicology and Pharmacology, 496–511 (2014). | spa |
| dc.relation.references | Huertas Méndez, N. D. J. et al. Synthetic Peptides Derived from Bovine Lactoferricin Exhibit Antimicrobial Activity against E. coli ATCC 11775, S. maltophilia ATCC 13636 and S. enteritidis ATCC 13076. Molecules, 1–10 (2017). | spa |
| dc.relation.references | Cárdenas-Martínez, K. J. et al. Effects of Substituting Arginine by Lysine in Bovine Lactoferricin Derived Peptides: Pursuing Production Lower Costs, Lower Hemolysis, and Sustained Antimicrobial Activity. Int J Pept Res Ther 1–12 (2021). | spa |
| dc.relation.references | De Both, N. J., Vermey, M., Dinjens, W. N., Bosman, F. T. A comparative evaluation of various invasion assays testing colon carcinoma cell lines. Br J Cancer, 934–941 (1999). | spa |
| dc.relation.references | Gheytanchi, E. et al. Morphological and molecular characteristics of spheroid formation in HT-29 and Caco-2 colorectal cancer cell lines. Cancer Cell Int, 1–16 (2021). | spa |
| dc.relation.references | Rousset, M. The human colon carcinoma cell lines HT-29 and Caco-2: Two in vitro models for the study of intestinal differentiation. Biochimie, 1035–1040 (1986). | spa |
| dc.relation.references | Ahmed, D. et al. Epigenetic and genetic features of 24 colon cancer cell lines. Oncogenesis, (2013). | spa |
| dc.relation.references | Hilchie, A. L., Vale, R., Zemlak, T. S., Hoskin, D. W. Generation of a hematologic malignancy-selective membranolytic peptide from the antimicrobial core (RRWQWR) of bovine lactoferricin. Exp Mol Pathol , 192–198 (2013). | spa |
| dc.relation.references | Kawai, K. et al. Comprehensive karyotyping of the HT-29 colon adenocarcinoma cell line. Genes Chromosomes Cancer, 1–8 (2002). | spa |
| dc.relation.references | Beter, M. et al. Multivalent Presentation of Cationic Peptides on Supramolecular Nanofibers for Antimicrobial Activity. Mol Pharm, 3660–3668 (2017). | spa |
| dc.relation.references | Zhang, F. et al. Short, mirror-symmetric antimicrobial peptides centered on “RRR” have broad-spectrum antibacterial activity with low drug resistance and toxicity. Acta Biomater, 145–167 (2022). | spa |
| dc.relation.references | Jia, B. Y. et al. High Cell Selectivity and Bactericidal Mechanism of Symmetric Peptides Centered on d-Pro–Gly Pairs. Int J Mol Sci, (2020). | spa |
| dc.relation.references | Yang, S. T., Shin, S. Y. & Kim, J. Il. Interaction mode of a symmetric Trp-rich undeca peptide PST11-RK with lipid bilayers. FEBS Lett, 157–163 (2007). | spa |
| dc.relation.references | Zhong, C. et al. Antimicrobial peptides with symmetric structures against multidrug-resistant bacteria while alleviating antimicrobial resistance. Biochem Pharmacol (2021). | spa |
| dc.relation.references | Vargas-Casanova, Y. et al. Palindromic Peptide LfcinB (21-25)Pal Exhibited Antifungal Activity against Multidrug-Resistant Candida. Chemistry Select, 7236–7242 (2020). | spa |
| dc.relation.references | Barragán-Cárdenas, A. C. et al. Changes in Length and Positive Charge of Palindromic Sequence RWQWRWQWR Enhance Cytotoxic Activity against Breast Cancer Cell Lines. ACS Omega, 2712–2722 (2022). | spa |
| dc.relation.references | Vargas-Casanova, Y. et al. Combining the Peptide RWQWRWQWR and an Ethanolic Extract of Bidens pilosa Enhances the Activity against Sensitive and Resistant Candida albicans and C. auris Strains. J Fungi, (2023). | spa |
| dc.relation.references | Svenson, J. et al. Metabolic fate of lactoferricin-based antimicrobial peptides: effect of truncation and incorporation of amino acid analogs on the in vitro metabolic stability. J Pharmacol Exp Ther, 1032–1039 (2010). | spa |
| dc.relation.references | Isidro-Llobet, A., Álvarez, M., Albericio, F. Amino acid-protecting groups. Chem Rev, 2455–2504 (2009). | spa |
| dc.relation.references | Alhassan, M., Kumar, A., Lopez, J., Albericio, F., de la Torre, B. G. Revisiting NO2 as Protecting Group of Arginine in Solid-Phase Peptide Synthesis. Int J Mol Sci, 1–12 (2020). | spa |
| dc.relation.references | Ragnarsson, U., Grehn, L. Dual protection of amino functions involving Boc. RSC Adv, 18691–18697 (2013). | spa |
| dc.relation.references | Applied Biosystems- ThermoFisher. Cleavage, Deprotection, and Isolation of Peptides after Fmoc Synthesis Potential Problems. | spa |
| dc.relation.references | GenScript. Peptide solubility Guidelines. https://www.genscript.com/peptide_solubility_and_stablity.html. | spa |
| dc.relation.references | Gutman, I. et al. Predicting the Success of Fmoc-Based Peptide Synthesis. ACS Omega, 23771–23781 (2022). | spa |
| dc.relation.references | GenScript. Recommended Peptide Purity Guidelines. https://www.genscript.com/recommended_peptide_purity.html. | spa |
| dc.relation.references | Mueller, L. K., Baumruck, A. C., Zhdanova, H., Tietze, A. A. Challenges and Perspectives in Chemical Synthesis of Highly Hydrophobic Peptides. Frontiers in Bioengineering and Biotechnology (2020). | spa |
| dc.relation.references | Peptide Hydrophobicity/Hydrophilicity Analysis Tool. https://www.peptide2.com/N_peptide_hydrophobicity_hydrophilicity.php. | spa |
| dc.relation.references | Zapadka, K. L., Becher, F. J., Gomes dos Santos, A. L. & Jackson, S. E. Factors affecting the physical stability (aggregation) of peptide therapeutics. Interface Focus (2017). | spa |
| dc.relation.references | Ertl, P. & Schuffenhauer, A. Estimation of synthetic accessibility score of drug-like molecules based on molecular complexity and fragment contributions. J Cheminform (2009). | spa |
| dc.relation.references | Peter M. Hwang, Ning Zhou, Xi Shan, Cheryl H. Arrowsmith, Hans J. Vogel. Three-Dimensional Solution Structure of Lactoferricin B, an Antimicrobial Peptide Derived from Bovine Lactoferrin†. Biochemistry, 4288–4298 (1998). | spa |
| dc.relation.references | Arbeláez, M. D. L. R., Aleixo, D. T., Barragán Cárdenas, A. C., Pittella, F., Tavares, G. D. The role of synthetic peptides derived from bovine lactoferricin against breast cancer cell lines: A mini-review. Oncologie, 629–633 (2023). | spa |
| dc.relation.references | Li, L., Vorobyov, I., Allen, T. W. The different interactions of lysine and arginine side chains with lipid membranes. Journal of Physical Chemistry B, 11906–11920 (2013). | spa |
| dc.relation.references | Hristova, K. & Wimley, W. C. A Look at Arginine in Membranes. J Membr Biol, 49 (2011). | spa |
| dc.relation.references | Khemaissa, S., Walrant, A., Sagan, S. Tryptophan, more than just an interfacial amino acid in the membrane activity of cationic cell-penetrating and antimicrobial peptides. Q Rev Biophys, (2022). | spa |
| dc.relation.references | Åmand, H. L., Fant, K., Nordén, B., Esbjörner, E. K. Stimulated endocytosis in penetratin uptake: Effect of arginine and lysine. Biochem Biophys Res Commun, 621–625 (2008). | spa |
| dc.relation.references | Yang, S.-T. et al. Selective cytotoxicity following Arg-to-Lys substitution in tritrpticin adopting a unique amphipathic turn structure. FEBS Lett, 229–233 (2003). | spa |
| dc.relation.references | Szabó, I. et al. Redesigning of Cell-Penetrating Peptides to Improve Their Efficacy as a Drug Delivery System. Pharmaceutics 2022, 907 (2022). | spa |
| dc.relation.references | Svenson, J. et al. Altered activity and physicochemical properties of short cationic antimicrobial peptides by incorporation of arginine analogues. Mol Pharm, 996–1005 (2009). | spa |
| dc.relation.references | Sahsuvar, S., Kocagoz, T., Gok, O., Can, O. In vitro efficacy of different PEGylation designs on cathelicidin-like peptide with high antibacterial and antifungal activity. Scientific Reports, 1–13 (2023). | spa |
| dc.relation.references | Greco, I. et al. Correlation between hemolytic activity, cytotoxicity and systemic in vivo toxicity of synthetic antimicrobial peptides. Sci Rep, (2020). | spa |
| dc.relation.references | Rodgers, G. M., Gilreath, J. A. The Role of Intravenous Iron in the Treatment of Anemia Associated with Cancer and Chemotherapy. Acta Haematol, 13–20 (2019). | spa |
| dc.relation.references | Timmons, P. B., Hewage, C. M. HAPPENN is a novel tool for hemolytic activity prediction for therapeutic peptides which employs neural networks. Scientific Reports, 1–18 (2020). | spa |
| dc.relation.references | Win, T. S. et al. HemoPred: a web server for predicting the hemolytic activity of peptides. Future Med Chem, 275–291 (2017). | spa |
| dc.relation.references | Askari, P., Namaei, M. H., Ghazvini, K., Hosseini, M. In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria. BMC Pharmacol Toxicol, 1–12 (2021). | spa |
| dc.relation.references | Takahashi S. et al. The Structure-Function Relationship of Mastoparan : Loss of the Hemolytic Activity of Mastoparan by Substituting Lysine with Ornithine Residues in the Molecule. The Journal of Tokyo Academy of Health Sciences, 86–96 (2002). | spa |
| dc.relation.references | Kang, A., Lee, J. H., Lin, E., Westerhoff, M. Metastatic colon carcinoma to the prostate gland. J Comput Assist Tomogr, 463–465 (2013). | spa |
| dc.relation.references | Insuasty-Cepeda, D. S. et al. Non-natural amino acids into LfcinB-derived peptides: effect in their (i) proteolytic degradation and (ii) cytotoxic activity against cancer cells. R Soc Open Sci (2023). | spa |
| dc.relation.references | Del Genio, V. et al. Peptides to Overcome the Limitations of Current Anticancer and Antimicrobial Nanotherapies. Pharmaceutics, (2022). | spa |
| dc.relation.references | Hollville, E., Martin, S. J. Measuring Apoptosis by Microscopy and Flow Cytometry. Curr Protoc Immunol (2016). | spa |
| dc.relation.references | Green, D. R., Llambi, F. Cell Death Signaling. Cold Spring Harb Perspect Biol (2015). | spa |
| dc.relation.references | Jan, R., Chaudhry, G. e. S. Understanding Apoptosis and Apoptotic Pathways Targeted Cancer Therapeutics. Adv Pharm Bull, 205 (2019). | spa |
| dc.relation.references | Vaseva, A. V., Moll, U. M. The mitochondrial p53 pathway. Biochim Biophys Acta, 414–420 (2009). | spa |
| dc.relation.references | Piatek, M., Sheehan, G., Kavanagh, K. Galleria mellonella: The Versatile Host for Drug Discovery, In Vivo Toxicity Testing and Characterising Host-Pathogen Interactions. Antibiotics, 1545 (2021). | spa |
| dc.relation.references | Ignasiak, K., Maxwell, A. Galleria mellonella (greater wax moth) larvae as a model for antibiotic susceptibility testing and acute toxicity trials. BMC Res Notes, 428 (2017). | spa |
| dc.relation.references | Erhirhie, E. O., Ihekwereme, C. P., Ilodigwe, E. E. Advances in acute toxicity testing: strengths, weaknesses and regulatory acceptance. Interdiscip Toxicol, 5–12 (2018). | spa |
| dc.relation.references | McCann, M. et al. In vitro and in vivo studies into the biological activities of 1,10-phenanthroline, 1,10-phenanthroline-5,6-dione and its copper(ii) and silver(i) complexes. Toxicol Res, 47–54 (2012). | spa |
| dc.relation.references | Perše, M. Cisplatin mouse models: Treatment, toxicity and translatability. Biomedicines (2021). | spa |
| dc.relation.references | Al Shoyaib, A., Archie, S. R., Karamyan, V. T. Intraperitoneal Route of Drug Administration: Should it Be Used in Experimental Animal Studies? Pharm Res, 12 (2019). | spa |
| dc.relation.references | Redfern, W. S. et al. The functional observational battery and modified Irwin test as global neurobehavioral assessments in the rat: Pharmacological validation data and a comparison of methods. J Pharmacol Toxicol Methods (2019). | spa |
| dc.relation.references | ICH S7A Safety pharmacology studies for human pharmaceuticals - Scientific guideline | European Medicines Agency. | spa |
| dc.relation.references | Zhao, X. et al. Optimized lactoferrin as a highly promising treatment for intracerebral hemorrhage: Pre-clinical experience. Journal of Cerebral Blood Flow & Metabolism (2021). | spa |
| dc.relation.references | Kumari, S., Ahsan, S. M., Kumar, J. M., Kondapi, A. K., Rao, N. M. Overcoming blood brain barrier with a dual purpose Temozolomide loaded Lactoferrin nanoparticles for combating glioma (SERP-17-12433). Scientific Reports, 1–13 (2017). | spa |
| dc.relation.references | Arcella, A. et al. In vitro and in vivo effect of human lactoferrin on glioblastoma growth. J Neurosurg, 1026–1035 (2015). | spa |
| dc.relation.references | Begley, D. J. Strategies for delivery of peptide drugs to the central nervous system: exploiting molecular structure. Journal of Controlled Release, 293–306 (1994). | spa |
| dc.relation.references | Qi, N. et al. Combined integrin αvβ3 and lactoferrin receptor targeted docetaxel liposomes enhance the brain targeting effect and anti-glioma effect. J Nanobiotechnology, 1–17 (2021). | spa |
| dc.relation.references | Caballero, M. V., Candiracci, M. Zebrafish as screening model for detecting toxicity and drugs efficacy. Journal of Unexplored Medical Data (2018). | spa |
| dc.relation.references | Chahardehi, A. M., Arsad, H., Lim, V. Zebrafish as a Successful Animal Model for Screening Toxicity of Medicinal Plants. Plants, 1–35 (2020). | spa |
| dc.relation.references | Brotzmann, K., Wolterbeek, A., Kroese, D., Braunbeck, T. Neurotoxic effects in zebrafish embryos by valproic acid and nine of its analogues: the fish-mouse connection? Arch Toxicol, 641–657 (2021). | spa |
| dc.rights.accessrights | info:eu-repo/semantics/openAccess | spa |
| dc.rights.license | Atribución-NoComercial-SinDerivadas 4.0 Internacional | spa |
| dc.subject.ddc | 540- Química y Ciencias Afines | spa |
| dc.subject.ddc | 570 - Biología::572 - Bioquímica | spa |
| dc.subject.lemb | Peptidos | spa |
| dc.subject.lemb | Cancer | spa |
| dc.subject.other | Lactoferrina | spa |
| dc.subject.proposal | Peptidos | spa |
| dc.subject.proposal | Lactoferricina bovina | spa |
| dc.subject.proposal | péptido hit | spa |
| dc.subject.proposal | péptido optimizado | spa |
| dc.subject.proposal | cáncer de colon | spa |
| dc.title | Síntesis y cribado de péptidos modificados derivados de lactoferricina bovina como fármacos citotóxicos contra líneas de cáncer de colon | spa |
| dc.title.translated | Synthesis and screening of modified peptides derived from bovine lactoferricin as cytotoxic drugs against colon cancer cell lines | eng |
| dc.type | Trabajo de grado - Doctorado | spa |
| dc.type.coar | http://purl.org/coar/resource_type/c_db06 | spa |
| dc.type.coarversion | http://purl.org/coar/version/c_ab4af688f83e57aa | spa |
| dc.type.content | Text | spa |
| dc.type.driver | info:eu-repo/semantics/doctoralThesis | spa |
| dc.type.redcol | http://purl.org/redcol/resource_type/TD | spa |
| dc.type.version | info:eu-repo/semantics/acceptedVersion | spa |
| dcterms.audience.professionaldevelopment | Bibliotecarios | spa |
| dcterms.audience.professionaldevelopment | Estudiantes | spa |
| dcterms.audience.professionaldevelopment | Investigadores | spa |
| dcterms.audience.professionaldevelopment | Público general | spa |
| oaire.accessrights | http://purl.org/coar/access_right/c_abf2 | spa |
| oaire.awardtitle | “Obtención de un prototipo peptídico promisorio para el desarrollo de un medicamento de amplio espectro para el tratamiento del cáncer de colon, cuello uterino y próstata” código 110184466986, contrato 845-2019. | spa |
| oaire.fundername | MinCiencias | spa |
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