Caracterización fisicoquímica de un péptido polivalente, derivado de la Lactoferricina Bovina, candidato a fármaco para el tratamiento del cáncer de mama

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dc.contributor.advisorRivera Monroy, Zuly Jenny
dc.contributor.advisorGonzález Cárdenas, Ivonne Alejandra
dc.contributor.authorHuertas Ortiz, Kevin Andrey
dc.contributor.researchgroupSíntesis y Aplicación de Moléculas Peptídicasspa
dc.date.accessioned2022-09-15T13:57:04Z
dc.date.available2022-09-15T13:57:04Z
dc.date.issued2021
dc.descriptiongráficas, ilustraciones, tablasspa
dc.description.abstractSegún la Organización Mundial de la Salud (OMS), el cáncer de mama es el tipo de cáncer más incidente entre las mujeres. Para el 2020 se reportaron cerca de 2,3 millones de nuevos casos de cáncer de mama y 685.000 muertes en el mundo fueron causadas por esta enfermedad. En la búsqueda de nuevos agentes terapéuticos, se ha propuesto el uso de péptidos polivalentes derivados de la Lactoferricina Bovina (LfcinB), y se han encontrado tres péptidos con actividad citotóxica frente a líneas celulares derivadas del cáncer de mama: el palíndromo LfcinB (21-25)Pal: RWQWRWQWR; el dímero [26F]-LficnB (20-30): (RRWQWRFKKLG)2K-Ahx y el tetrámero LfcinB (20-25)4: ((RRWQWR)2K-Ahx-C)2. Para desarrollo de un medicamento, una etapa crucial en la fase cero de los estudios preclínicos es la caracterización fisicoquímica de la molécula que presenta actividad promisoria, esta fase involucra la implementación y validación de los métodos que serán utilizados para el análisis de la molécula. Esta investigación fue conducida dentro de este contexto, y se seleccionó el péptido tetramérico LfcinB (20-25)4 como molécula modelo. Específicamente: (i) se sintetizó un lote de 100 mg del péptido LfcinB (20-25)4, (ii) se desarrolló y optimizó un método de análisis de péptidos sintéticos por RP-HPLC, (iii) se caracterizó el péptido LfcinB (20-25)4 mediante RMN (1D-2D) y espectrometría de masas (ESI-Q, ESI-QTOF, MALDI-TOF). Adicionalmente, (iv) se analizó en el lote el contenido de agua por Karl Fischer, el contenido de TFA residual por HPLC-DAD y el contenido del péptido por RP- X HPLC-DAD, estas tres metodologías de cuantificación fueron validadas siguiendo los lineamientos de la USP capítulo <1225>. Las metodologías de análisis implementadas, desarrolladas y validadas en esta tesis contribuyen a la caracterización fisicoquímica de péptidos promisorios como agentes terapéuticos. (Texto tomado de la fuente)spa
dc.description.abstractAccording to World Health Organization, breast cancer is the most common cancer type among women. In 2020, around 2,3 million of new cases of breast cancer were reported and 685.000 of deaths were caused by this disease. In the search of new therapeutic agents, polyvalent peptides derived from Bovine Lactoferricin (LfcinB) were proposed. Three peptides were found with cytotoxic activity against breast cancer cell lines: palindrome RWQWRWQWR; dimer (RRWQWRFKKLG)2K-Ahx and tetramer LfcinB (20-25)4: ((RRWQWR)2K-Ahx-C)2. One of the crucial steps on the zero-phase of preclinical studies, for development of a new drug, is the physicochemical characterization of the molecule with promissory activity. This phase involves implementation and validation of methods that shall be used for the analysis of the molecule. This research was conducted within this context, and the tetrameric peptide LfcinB (20-25)4 was selected as model molecule. Specifically: (i) a batch of 100 mg of peptide LfcinB (20- 25)4 was synthetized, (ii) a method for the analysis of peptides by RP-HPLC was developed and optimized, (iii) peptide LfcinB (20-25)4 was characterized by NMR (1D-2) and mass spectrometry (ESI-Q, ESI-QTOF, MALDI-TOF). In addition, (iv) water content by Karl Fischer, TFA content by HPLC-DAD and peptide content by RP-HPLC-DAD were analyzed in the batch of peptide; these three quantitation methodologies were validated according to USP guidelines in chapter <1225>. The analytical methodologies implemented, developed, and validated on this thesis contribute to physicochemical characterization of promissory peptides as therapeutic agentseng
dc.description.degreelevelMaestríaspa
dc.description.degreenameMagíster en Ciencias - Químicaspa
dc.description.researchareaQuímica Analíticaspa
dc.format.extentxxiv, 134 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/82290
dc.language.isospaspa
dc.publisherUniversidad Nacional de Colombiaspa
dc.publisher.branchUniversidad Nacional de Colombia - Sede Bogotáspa
dc.publisher.departmentDepartamento de Químicaspa
dc.publisher.facultyFacultad de Cienciasspa
dc.publisher.placeBogotá, Colombiaspa
dc.publisher.programBogotá - Ciencias - Maestría en Ciencias - Químicaspa
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dc.rights.accessrightsinfo:eu-repo/semantics/openAccessspa
dc.rights.licenseReconocimiento 4.0 Internacionalspa
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/spa
dc.subject.ddc540 - Química y ciencias afines::543 - Química analíticaspa
dc.subject.lembNeoplasmasspa
dc.subject.lembNeoplasmseng
dc.subject.lembCancerspa
dc.subject.lembCáncereng
dc.subject.proposalpéptidos anticáncerigenosspa
dc.subject.proposalvalidaciónspa
dc.subject.proposalcaracterización fisicoquímicaspa
dc.subject.proposalagentes terapéuticosspa
dc.subject.proposalHPLCspa
dc.subject.proposalEspectrometría de masasspa
dc.subject.proposalTherapeutic peptideseng
dc.subject.proposalvalidationeng
dc.subject.proposalphysicochemical characterizationeng
dc.subject.proposaltherapeutic agentseng
dc.subject.proposalHPLCeng
dc.subject.proposalMass spectrometryeng
dc.titleCaracterización fisicoquímica de un péptido polivalente, derivado de la Lactoferricina Bovina, candidato a fármaco para el tratamiento del cáncer de mamaspa
dc.title.translatedPhysicochemical characterization of a polyvalent peptide, derived from Bovine Lactoferricin, drug candidate for breast cancer treatmenteng
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.contentDataPaperspa
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
oaire.awardtitleDesarrollo de un medicamento contra el cáncer de mama basado en un péptido polivalente derivado de la LfcinB - Estudio de la fase preclínica (fase cero): caracterización fisicoquímica de un lote del fármaco para estudios pre-clínicosspa
oaire.fundernameMINCIENCIASspa

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