Caracterización fisicoquímica de péptidos sintéticos monoméricos y diméricos derivados de la Lactoferricina Bovina con actividad anticancerígena comprobada

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dc.contributor.advisorGarcía Castañeda, Javier Eduardo
dc.contributor.advisorMartínez Ramírez, Jorge Ariel
dc.contributor.authorGonzález López, Nicolás Mateo
dc.contributor.orcidNicolás Mateo González López [0000-0003-0009-1347]spa
dc.contributor.researchgroupSíntesis y Aplicación de Moléculas Peptídicasspa
dc.date.accessioned2023-08-01T17:34:10Z
dc.date.available2023-08-01T17:34:10Z
dc.date.issued2023
dc.descriptionilustraciones, diagramasspa
dc.description.abstractSegún la OMS el cáncer es una de las causas principales de muerte a nivel mundial, presentándose 10 millones de fallecimientos en el 2020. Las terapias para el manejo contra el cáncer son agresivas, poco selectivas y producen efectos adversos que afectan la calidad de vida del paciente. Esto ha generado la necesidad de desarrollar nuevos tratamientos contra el cáncer que sean seguros y eficaces. En la actualidad los péptidos han surgido como una alternativa terapéutica para el tratamiento de enfermedades, sin embargo, debido a que cada péptido posee propiedades fisicoquímicas únicas, hace que su caracterización analítica represente grandes retos, y esto hace que sea una etapa clave en el desarrollo de medicamentos. En este trabajo se desarrollaron e implementaron metodologías analíticas siguiendo las recomendaciones de las farmacopeas USP y europea para caracterizar péptidos utilizando como modelo experimental los péptidos anticancerígenos: RWQWRWQWR y (RRWQWRFKKLG)2-K-Ahx, los cuales se consideran promisorios para el desarrollo de un medicamento de amplio espectro contra el cáncer. Se realizó el escalamiento de la síntesis de los dos péptidos obteniendo tres lotes de aproximadamente 10, 50 y 100 mg de péptido puro (Capítulo 1) con el objetivo de determinar si el escalamiento del proceso sintético afectaba las propiedades fisicoquímicas del fármaco. Se desarrollaron e implementaron metodologías de análisis por RP-HPLC (Capítulo 2) y LC-MS (Capítulo 3) para confirmar su identidad. Los métodos de RP-HPLC desarrollados pueden ser utilizados para identificar y/o cuantificar péptidos con un amplio rango de hidrofobicidad/hidrofilicidad en mezclas complejas o provenientes de matrices biológicas. Se empleó espectroscopía RMN para caracterizar ambos péptidos (Capítulo 4), se modelaron sus propiedades fisicoquímicas utilizando herramientas bioinformáticas (Capítulo 5). Se desarrolló e implementó un método para determinar el contenido de péptido en cada lote empleando IS y evaluándolos a 280nm (Capítulo 6). Se identificó y cuantifico los péptidos en el medio de cultivo de la línea celular HeLa (Capítulo 9). Finalmente, se caracterizó cada péptido por FT-IR y se empleó esta técnica para implementar y monitorear el cambio del contraión trifluoroacetato a clorhidrato. (Capítulos 7 y 8). Las metodologías desarrolladas en este trabajo pueden ser aplicadas para la caracterización fisicoquímica de péptidos monoméricos o diméricos. Estas metodologías son versátiles y de amplia cobertura por lo que se pueden utilizar para caracterizar péptidos con diversas propiedades fisicoquímicas. (Texto tomado de la fuente)spa
dc.description.abstractAccording to the WHO cancer is one of the leading causes of death worldwide, with 10 million deaths in 2020. The therapies for cancer management are aggressive, non-selective, and produce adverse effects that affect the quality of life of the patient. This has generated the need to develop new cancer treatments that are safe and effective. Currently, peptides have emerged as a therapeutic alternative for the treatment of diseases, however, since each peptide has unique physicochemical properties, its analytical characterization represents a great challenge and is a key stage in drug development. In this work, analytical methodologies recommended by the USP, and European pharmacopeias will be developed and implemented to characterize the anticancer peptides: RWQWRWQWR and (RRWQWRFKKLG)2-K-Ahx, which are considered promising for the development of a broad-spectrum cancer drug. The synthesis of the two peptides was scaled up, obtaining three batches of approximately 10, 50 and 100 mg of pure peptide (Chapter 1) with the objective of determining if the scaling up of the synthetic process affected the physicochemical properties of the drug. Analytical methodologies by RP-HPLC (Chapter 2) and LC-MS (Chapter 3) were developed to confirm their identity. The developed RP-HPLC methods can be used to identify and/or quantify peptides with a wide range of hydrophobicity/hydrophilicity in complex mixtures or from biological matrices. NMR was used to structurally characterize both peptides (Chapter 4). Their physicochemical properties were modeled using bioinformatics tools (Chapter 5). A method was developed and implemented to determine the peptide content in the batches using IS and evaluating them at 280nm (Chapter 6). Peptides were identified and quantified in the culture medium of the HeLa cell line (Chapter 9). Finally, each peptide was characterized by FT-IR and this technique was also used to monitor the change of the counterion trifluoroacetate to hydrochloride. (Chapters 7 and 8). The methodologies developed in this work can be applied for the physicochemical characterization of monomeric or dimeric peptides. These methodologies are versatile and have a wide coverage, so they can be used to characterize peptides with diverse physicochemical properties.eng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagister en Ciencias Farmacéuticasspa
dc.description.researchareaAnálisis Farmacéuticospa
dc.format.extentxx, 101 páginasspa
dc.format.mimetypeapplication/pdfspa
dc.identifier.instnameUniversidad Nacional de Colombiaspa
dc.identifier.reponameRepositorio Institucional Universidad Nacional de Colombiaspa
dc.identifier.repourlhttps://repositorio.unal.edu.co/spa
dc.identifier.urihttps://repositorio.unal.edu.co/handle/unal/84397
dc.language.isospaspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.facultyFacultad de Cienciasspa
dc.publisher.placeBogotá, Colombiaspa
dc.publisher.programBogotá - Ciencias - Maestría en Ciencias Farmacéuticasspa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseAtribución-NoComercial-SinDerivadas 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/spa
dc.subject.agrovocPéptidos sintéticosspa
dc.subject.agrovocSynthetic peptideseng
dc.subject.ddc540 - Química y ciencias afines::543 - Química analíticaspa
dc.subject.ddc500 - Ciencias naturales y matemáticas::502 - Misceláneaspa
dc.subject.ddc610 - Medicina y salud::615 - Farmacología y terapéuticaspa
dc.subject.ddc540 - Química y ciencias afines::542 - Técnicas, procedimientos, aparatos, equipos, materialesspa
dc.subject.lembCANCER-TRATAMIENTOspa
dc.subject.lembCancer-treatmenteng
dc.subject.proposalPéptidos Anticancerígenosspa
dc.subject.proposalLactoferricina Bovinaspa
dc.subject.proposalMetodologías Analíticasspa
dc.subject.proposalFarmacopeaspa
dc.subject.proposalCaracterización Analíticaspa
dc.subject.proposalPropiedades Fisicoquímicasspa
dc.subject.proposalAnticancer Peptideseng
dc.subject.proposalBovine Lactoferricineng
dc.subject.proposalAnalytical Methodologieseng
dc.subject.proposalPharmacopoeiaeng
dc.subject.proposalAnalytical Characterizationeng
dc.subject.proposalPhysicochemical Propertieseng
dc.titleCaracterización fisicoquímica de péptidos sintéticos monoméricos y diméricos derivados de la Lactoferricina Bovina con actividad anticancerígena comprobadaspa
dc.title.translatedPhysicochemical characterization of monomeric and dimeric synthetic peptides derived from Bovine Lactoferricin with proven anticancer activityeng
dc.typeTrabajo de grado - Maestríaspa
dc.type.coarhttp://purl.org/coar/resource_type/c_bdccspa
dc.type.coarversionhttp://purl.org/coar/version/c_ab4af688f83e57aaspa
dc.type.contentTextspa
dc.type.driverinfo:eu-repo/semantics/masterThesisspa
dc.type.redcolhttp://purl.org/redcol/resource_type/TMspa
dc.type.versioninfo:eu-repo/semantics/acceptedVersionspa
dcterms.audience.professionaldevelopmentEstudiantesspa
dcterms.audience.professionaldevelopmentInvestigadoresspa
dcterms.audience.professionaldevelopmentMaestrosspa
dcterms.audience.professionaldevelopmentPúblico generalspa
oaire.accessrightshttp://purl.org/coar/access_right/c_abf2spa

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