Caracterización fisicoquímica de un péptido polivalente, derivado de la Lactoferricina Bovina, candidato a fármaco para el tratamiento del cáncer de mama
gráficas, ilustraciones, tablas
- Autores:
-
Huertas Ortiz, Kevin Andrey
- Tipo de recurso:
- Fecha de publicación:
- 2021
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/82290
- Palabra clave:
- 540 - Química y ciencias afines::543 - Química analítica
Neoplasmas
Cancer
Neoplasms
Cáncer
péptidos anticáncerigenos
validación
caracterización fisicoquímica
agentes terapéuticos
HPLC
Espectrometría de masas
Therapeutic peptides
validation
physicochemical characterization
therapeutic agents
HPLC
Mass spectrometry
- Rights
- openAccess
- License
- Reconocimiento 4.0 Internacional
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Caracterización fisicoquímica de un péptido polivalente, derivado de la Lactoferricina Bovina, candidato a fármaco para el tratamiento del cáncer de mama |
| dc.title.translated.eng.fl_str_mv |
Physicochemical characterization of a polyvalent peptide, derived from Bovine Lactoferricin, drug candidate for breast cancer treatment |
| title |
Caracterización fisicoquímica de un péptido polivalente, derivado de la Lactoferricina Bovina, candidato a fármaco para el tratamiento del cáncer de mama |
| spellingShingle |
Caracterización fisicoquímica de un péptido polivalente, derivado de la Lactoferricina Bovina, candidato a fármaco para el tratamiento del cáncer de mama 540 - Química y ciencias afines::543 - Química analítica Neoplasmas Cancer Neoplasms Cáncer péptidos anticáncerigenos validación caracterización fisicoquímica agentes terapéuticos HPLC Espectrometría de masas Therapeutic peptides validation physicochemical characterization therapeutic agents HPLC Mass spectrometry |
| title_short |
Caracterización fisicoquímica de un péptido polivalente, derivado de la Lactoferricina Bovina, candidato a fármaco para el tratamiento del cáncer de mama |
| title_full |
Caracterización fisicoquímica de un péptido polivalente, derivado de la Lactoferricina Bovina, candidato a fármaco para el tratamiento del cáncer de mama |
| title_fullStr |
Caracterización fisicoquímica de un péptido polivalente, derivado de la Lactoferricina Bovina, candidato a fármaco para el tratamiento del cáncer de mama |
| title_full_unstemmed |
Caracterización fisicoquímica de un péptido polivalente, derivado de la Lactoferricina Bovina, candidato a fármaco para el tratamiento del cáncer de mama |
| title_sort |
Caracterización fisicoquímica de un péptido polivalente, derivado de la Lactoferricina Bovina, candidato a fármaco para el tratamiento del cáncer de mama |
| dc.creator.fl_str_mv |
Huertas Ortiz, Kevin Andrey |
| dc.contributor.advisor.none.fl_str_mv |
Rivera Monroy, Zuly Jenny González Cárdenas, Ivonne Alejandra |
| dc.contributor.author.none.fl_str_mv |
Huertas Ortiz, Kevin Andrey |
| dc.contributor.researchgroup.spa.fl_str_mv |
Síntesis y Aplicación de Moléculas Peptídicas |
| dc.subject.ddc.spa.fl_str_mv |
540 - Química y ciencias afines::543 - Química analítica |
| topic |
540 - Química y ciencias afines::543 - Química analítica Neoplasmas Cancer Neoplasms Cáncer péptidos anticáncerigenos validación caracterización fisicoquímica agentes terapéuticos HPLC Espectrometría de masas Therapeutic peptides validation physicochemical characterization therapeutic agents HPLC Mass spectrometry |
| dc.subject.lemb.spa.fl_str_mv |
Neoplasmas Cancer |
| dc.subject.lemb.eng.fl_str_mv |
Neoplasms Cáncer |
| dc.subject.proposal.spa.fl_str_mv |
péptidos anticáncerigenos validación caracterización fisicoquímica agentes terapéuticos HPLC Espectrometría de masas |
| dc.subject.proposal.eng.fl_str_mv |
Therapeutic peptides validation physicochemical characterization therapeutic agents HPLC Mass spectrometry |
| description |
gráficas, ilustraciones, tablas |
| publishDate |
2021 |
| dc.date.issued.none.fl_str_mv |
2021 |
| dc.date.accessioned.none.fl_str_mv |
2022-09-15T13:57:04Z |
| dc.date.available.none.fl_str_mv |
2022-09-15T13:57:04Z |
| dc.type.spa.fl_str_mv |
Trabajo de grado - Maestría |
| dc.type.driver.spa.fl_str_mv |
info:eu-repo/semantics/masterThesis |
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info:eu-repo/semantics/acceptedVersion |
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DataPaper |
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http://purl.org/redcol/resource_type/TM |
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acceptedVersion |
| dc.identifier.uri.none.fl_str_mv |
https://repositorio.unal.edu.co/handle/unal/82290 |
| dc.identifier.instname.spa.fl_str_mv |
Universidad Nacional de Colombia |
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Repositorio Institucional Universidad Nacional de Colombia |
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https://repositorio.unal.edu.co/ |
| url |
https://repositorio.unal.edu.co/handle/unal/82290 https://repositorio.unal.edu.co/ |
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Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia |
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spa |
| language |
spa |
| dc.relation.references.spa.fl_str_mv |
WHO. World Health Organization - Cancer [Internet]. 2020. Available from: https://www.who.int/news-room/fact-sheets/detail/cancer Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;0(0):1–41. Huertas N de J, Monroy ZJR, Medina RF, Castañeda JEG. Antimicrobial Activity of Truncated and Polyvalent Peptides Derived from the FKCRRQWQWRMKKGLA Sequence against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923. Molecules. 2017;22(6). Huertas Méndez NDJ, Vargas Casanova Y, Gómez Chimbi AK, Hernández E, Leal Castro AL, Melo Diaz JM, 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. 2017;22(3):1–10. León-Calvijo MA, Leal-Castro AL, Almanzar-Reina GA, Rosas-Pérez JE, García-Castañeda JE, Rivera-Monroy ZJ. Antibacterial activity of synthetic peptides derived from lactoferricin against Escherichia coli ATCC 25922 and Enterococcus Faecalis ATCC 29212. Biomed Res Int. 2015;2015:1DUMMY. Vargas Casanova Y, Rodríguez Guerra JA, Umaña Pérez YA, Leal Castro AL, Almanzar Reina G, García Castañeda JE, 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. 2017;22(10):1–11. United THE, Pharmacopeia S. 2018 USP 41. Vol. 5. 2018. Janvier S, Sutter E De, Wynendaele E, Spiegeleer B De, Vanhee C, Deconinck E. Talanta Analysis of illegal peptide drugs via HILIC-DAD-MS. Talanta [Internet]. 2017;174(June):562–71. Available from: http://dx.doi.org/10.1016/j.talanta.2017.06.034 Mutalik S, Hewavitharana AK, Shaw PN, Anissimov YG, Roberts MS, Parekh HS. Development and validation of a reversed-phase high-performance liquid chromatographic method for quantification of peptide dendrimers in human skin permeation experiments. 2009;877:3556–62. Anaya K, Sus N, Gadelha C, Frank J. Development and validation of a rapid reversed ‑ phase liquid chromatography method for CnAMP1 peptide quantification in human intestinal cell lines. Amino Acids [Internet]. 2019;51(3):407–18. Available from: https://doi.org/10.1007/s00726-018-2675-7 Egusquiaguirre SP, Manguán-garcía C, Perona R, Luís J, Maria R, Igartua M. Development and validation of a rapid HPLC method for the quantification of GSE4 peptide in biodegradable PEI – PLGA nanoparticles. J Chromatogr B [Internet]. 2014;972:95–101. Available from: http://dx.doi.org/10.1016/j.jchromb.2014.09.041 Instituto Nacional del Cáncer. Cáncer de seno (mama) [Internet]. 2019. Available from: https://www.cancer.gov/espanol/tipos/seno Salvatierra-González R, Benguigui Y. Resistencia antimicrobiana en las Américas: Magnitud del problema y su contención. Organ Panam la Salud, Of Sanit Panam Of Reg la Organ Mund la Salud. 2000; Castañeda-casimiro J, Ortega-roque JA, Marcela A, Aquino-andrade A, Serafín-lópez J, Estrada-parra S, et al. Péptidos antimicrobianos: péptidos con múltiples funciones. Alergia, asma e Inmunol [Internet]. 2009;18(1):16–29. Available from: http://www.medigraphic.com/pdfs/alergia/al-2009/al091d.pdf Barragán-Cárdenas A, Insuasty-Cepeda DS, Niño-Ramírez VA, Umaña-Pérez A, Ochoa-Zarzosa A, López-Meza JE, et al. The Nonapeptide RWQWRWQWR: A Promising Molecule for Breast Cancer Therapy. ChemistrySelect. 2020;5(31):9691–700. Barragán-Cárdenas A, Urrea-Pelayo M, Niño-Ramírez VA, Umaña-Pérez A, Vernot JP, Parra-Giraldo CM, 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. 2020;10(30):17593–601. Guerra JR, Cárdenas AB, Ochoa-Zarzosa A, Meza JL, Umaña Pérez A, Fierro-Medina 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. 2019;9(36):20497–504. Kunda NK. Antimicrobial peptides as novel therapeutics for non-small cell lung cancer. Drug Discov Today [Internet]. 2020;25(1):238–47. Available from: https://doi.org/10.1016/j.drudis.2019.11.012 Gifford JL, Hunter HN, Vogel HJ. Lactoferricin: A lactoferrin-derived peptide with antimicrobial, antiviral, antitumor and immunological properties. Cell Mol Life Sci. 2005;62(22):2588–98. Bruni N, Capucchio MT, Biasibetti E, Pessione E, Cirrincione S, Giraudo L, et al. Antimicrobial activity of lactoferrin-related peptides and applications in human and veterinary medicine. Molecules. 2016;21(6). Schibli DJ, Hwang PM, Vogel HJ. The structure of the antimicrobial active center of lactoferricin B bound to sodium dodecyl sulfate micelles. FEBS Lett. 1999;446(2–3):213–7. Insuasty-Cepeda DS, Barragán-Cárdenas AC, Ochoa-Zarzosa A, López-Meza JE, Fierro-Medina R, García-Castañeda JE, 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. 2020;21(12):1–13. Andersson L, Blomberg L, Flegel M, Lepsa L, Nilsson B, Verlander M. Large-scale synthesis of peptides. Biopolym - Pept Sci Sect. 2000;55(3):227–50. Zompra AA, Galanis AS, Werbitzky O, Albericio F. Manufacturing peptides as active pharmaceutical ingredients. Future Med Chem. 2009;1(2):361–77. Ardila-Chantré N, Hernández-Cardona AK, Pineda-Castañeda HM, Estupiñan-Torres SM, Leal-Castro AL, Fierro-Medina R, et al. Short peptides conjugated to non-peptidic motifs exhibit antibacterial activity. RSC Adv. 2020;10(49):29580–6. Insuasty Cepeda D, Pineda Castañeda H, Rodríguez Mayor A, García Castañeda J, Maldonado Villamil M, Fierro Medina R, et al. Synthetic Peptide Purification via Solid-Phase Extraction with Gradient Elution: A Simple, Economical, Fast, and Efficient Methodology. Molecules [Internet]. 2019;24(7):1215. Available from: https://www.mdpi.com/1420-3049/24/7/1215 FDA-U.S. Department of Health and Human Services. Analytical Procedures and Methods Validation for Drugs and Biologics. Guid Ind. 2015;(July):1–15. Aguirre, L E al. Validación de Métodos Analíticos. Barcelona: AEFI; 2001. AOAC. How to Meet ISO 17025 Requirements for Method Verification. ALACC Guid. 2007; ICH-Harmonised-tripartite-guideline. Validation of Analytical Procedures : Text and Methodology, Q2 (R1), Geneva. Int Conf Harmon. 2005;1994(October 1994):1–17. Magnusson B, Örnemark U. Eurachem Guide: The Fitness for Purpose of Analytical Methods - A Laboratory Guide to Method Validation and Related Topics. 2nd ed. Eurachem. 2014. 62 p. ISO 5725-1:1994 Accuracy (trueness and precision) of measurement methods and results - Part 1: General principles and definitions. In 1994. JCGM 200:2012 International vocabulary of metrology - Basic and general concepts and associated terms (VIM). 2012. 91 p. The Global Cancer Observatory [Internet]. World Health Organization. 2018. Available from: https://gco.iarc.fr/today/home Terrasse V. Latest global cancer data: Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018 [Internet]. 2018. Available from: https://www.iarc.fr/wp-content/uploads/2018/09/pr263_E.pdf Organization WH. Globocan Colombia Fact Sheet. 2018;1–2. Available from: https://gco.iarc.fr/today/data/factsheets/populations/170-colombia-fact-sheets.pdf Bustamante Rojas C. Fases del desarrollo de un nuevo medicamento. 2013;1–4. Available from: http://clinicalevidence.pbworks.com/w/file/fetch/63221078/FASES DE DESARROLL%0AO.pdf Atkinson A. Principles of Clinical Pharmacology. Second Edi. 2007. 501–505 p. Roux S, Zékri E, Rousseau B, Cintrat JC, Fay N. Elimination and exchange of trifluoroacetate counter-ion from cationic peptides: A critical evaluation of different approaches. J Pept Sci. 2008;14(3):354–9. Thermo. Application Note 115 Determination of Trifluoroacetic Acid ( TFA ) in Peptides. :1–6. Wujcik CE, Cahill TM, Seiber JN. Extraction and Analysis of Trifluoroacetic Acid in Environmental Waters. Anal Chem. 1998;70(19):4074–80. Cahill TM, Benesch JA, Gustin MS, Zimmerman EJ, Seiber JN. Simplified method for trace analysis of trifluoroacetic acid in plant, soil and water samples using headspace gas chromatography. ACS Div Environ Chem Prepr. 1999;39(2):15–7. Johnson M, Liu M, Struble E, Hettiarachchi K. Characterization of cyclic peptides containing disulfide bonds. J Pharm Biomed Anal [Internet]. 2015;109:112–20. Available from: http://dx.doi.org/10.1016/j.jpba.2015.01.009 Anthis NJ, Clore GM. Sequence-specific determination of protein and peptide concentrations by absorbance at 205 nm. Protein Sci. 2013;22(6):851–8. Moffatt F, Senkans P, Ricketts D. Approaches towards the quantitative analysis of peptides and proteins by reversed-phase high-performance liquid chromatography in the absence of a pure reference sample. J Chromatogr A. 2000;891(2):235–42. McNaught A, Wilkinson A. IUPAC the Gold Book [Internet]. 2019. p. 1. Available from: https://goldbook.iupac.org/terms/view/I03089 Vanhee C, Janvier S, Desmedt B, Moens G, Deconinck E, Beer O De, et al. Talanta Analysis of illegal peptide biopharmaceuticals frequently encountered by controlling agencies. Talanta [Internet]. 2015;142:1–10. Available from: http://dx.doi.org/10.1016/j.talanta.2015.04.022 Stahl M. Peak purity analysis in HPLC and CE using diode-array technology. Agil Technol [Internet]. 2003;8:5988–8647. Available from: http://www.agilent.com/cs/library/applications/5988-8647EN.pdf (Accessed on 24 April 2016) FDA. Methods, Method Verification and Validation. ORA Lab Proced. 2014;II:1–19. Vander Heyden Y, Nijhuis A, Smeyers-Verbeke J, Vandeginste BGM, Massart DL. Guidance for robustness/ruggedness tests in method validation. J Pharm Biomed Anal. 2001;24(5–6):723–53. Myers R, Montgomery DC, Anderson-Cook CM. Response Surface Methodology: Process and Product Optimization Using Designed Experiments. 4th ed. Hoboken, New Jersey: John Wiley & Sons; 2016. 825 p. Müller A, Flottmann D, Schulz W, Seitz W, Weber WH. Assessment of robustness for an LC-MS-MS multi-method by response-surface methodology, and its sensitivity. Anal Bioanal Chem. 2008;390(5):1317–26. Li W, Zhao LC, Wang Z, Zheng YN, Liang J, Wang H. Response surface metodology to optimize enzymatic preparation of deapio-platycodin D and platycodin D from radix platycodi. Int J Mol Sci. 2012;13(4):4089–100. Sarabia LA, Ortiz MC. Response Surface Methodology. Comprehensive Chemometrics. 2009;345–90. Agrawal R, Belemkar S, Bonde C. A Stepwise Strategy Employing Automated Screening for Reversed-Phase Chromatographic Separation of Itraconazole and Its Impurities. Chromatographia [Internet]. 2019;82(12):1767–75. Available from: https://doi.org/10.1007/s10337-019-03802-0 Dolan JW. System Suitability. LCGC North Am. 2009;27(12):1040–4. van Deemter JJ, Klinkenberg A, Zuiderweg FJ. Longitudinal diffusion and resistance to mass transfer as causes of nonideality in chromatography. Chem Eng Sci. 1956;5(6):271–89. Gritti F, Guiochon G. The van Deemter equation: Assumptions, limits, and adjustment to modern high performance liquid chromatography. J Chromatogr A [Internet]. 2013;1302:1–13. Available from: http://dx.doi.org/10.1016/j.chroma.2013.06.032 Hawkes SJ. Modernization of the van Deemter equation for chromatographic zone dispersion. 1983;60(May):393–8. DeStefano JJ, Schuster SA, Lawhorn JM, Kirkland JJ. Performance characteristics of new superficially porous particles. J Chromatogr A [Internet]. 2012;1258:76–83. Available from: http://dx.doi.org/10.1016/j.chroma.2012.08.036 González-Ruiz V, Olives AI, Martín MA. Core-shell particles lead the way to renewing high-performance liquid chromatography. TrAC - Trends Anal Chem [Internet]. 2015;64:17–28. Available from: http://dx.doi.org/10.1016/j.trac.2014.08.008 Fekete S, Ganzler K, Fekete J. Efficiency of the new sub-2μm core-shell (KinetexTM) column in practice, applied for small and large molecule separation. J Pharm Biomed Anal. 2011;54(3):482–90. Desmet G, Clicq D, Gzil P. Geometry-independent plate height representation methods for the direct comparison of the kinetic performance of LC supports with a different size or morphology. Anal Chem. 2005;77(13):4058–70. Desmet G, Clicq D, Nguyen DTT, Guillarme D, Rudaz S, Veuthey JL, et al. Practical constraints in the kinetic plot representation of chromatographic performance data: Theory and application to experimental data. Anal Chem. 2006;78(7):2150–62. Broeckhoven K, Cabooter D, Desmet G. Kinetic performance comparison of fully and superficially porous particles with sizes ranging between 2.7 μm and 5 μm: Intrinsic evaluation and application to a pharmaceutical test compound. J Pharm Anal [Internet]. 2013;3(5):313–23. Available from: http://dx.doi.org/10.1016/j.jpha.2012.12.006 Broeckhoven K, Cabooter D, Eeltink S, Desmet G. Kinetic plot based comparison of the efficiency and peak capacity of high-performance liquid chromatography columns: Theoretical background and selected examples. J Chromatogr A [Internet]. 2012;1228:20–30. Available from: http://dx.doi.org/10.1016/j.chroma.2011.08.003 Broeckhoven K, Cabooter D, Lynen F, Sandra P, Desmet G. The kinetic plot method applied to gradient chromatography: Theoretical framework and experimental validation. J Chromatogr A [Internet]. 2010;1217(17):2787–95. Available from: http://dx.doi.org/10.1016/j.chroma.2010.02.023 Snyder LR, Kirkland JJ, Dolan JW. Introduction to Modern Liquid Chromatography. 3rd ed. New Jersey: John Wiley & Sons; 2010. 960 p. Snyder LR, Dolan JW. High-performance gradient elution: the practical application of the linear-solvent-strength model. New Jersey: John Wiley & Sons; 2007. 496 p. Meyer VR. Practical High Performance Liquid Chromatography. 5th ed. Chichester: John Wiley & Sons; 2010. 432 p. Aguilar M. HPLC of Peptides and Proteins [Internet]. Vol. 251, Methods in Molecular Biology. 2004. 3–8 p. Available from: http://www.ncbi.nlm.nih.gov/pubmed/14704444 Dolan JW. Method Adjustment for Gradient Elution. LCGC North America. 2017;480–5. Yang Y. Peptide Global Deprotection/Scavenger-Induced Side Reactions. Side Reactions in Peptide Synthesis. 2016. 43–75 p. Mohammad M, Motalib A, Afrina A, Salahuddin KM, Mashud SM, Sharif A. Method Validation for the Determination of Water Content of Metered Dose Inhaler By Karl Fischer Coulometer. Int Res J Pharm. 2012;3(7):144–7. AOAC. Guidelines for Standard Method Performance Requirements. J AOAC Int Off Method Anal. 2016;9. Daniel C. Use of Half-Normal Plots in Interpreting Factorial Two-Level Experiments. Technometrics. 1959;1(4):311. |
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Reconocimiento 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Rivera Monroy, Zuly Jennybcc909fcc85ff0efa659b7aaca42b3cbGonzález Cárdenas, Ivonne Alejandra389848782c24051d9390c33ea5a4db31Huertas Ortiz, Kevin Andrey35e52b870be748a12efb60f838186b9cSíntesis y Aplicación de Moléculas Peptídicas2022-09-15T13:57:04Z2022-09-15T13:57:04Z2021https://repositorio.unal.edu.co/handle/unal/82290Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/gráficas, ilustraciones, tablasSegún 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)According 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 agentsMaestríaMagíster en Ciencias - QuímicaQuímica Analíticaxxiv, 134 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Ciencias - Maestría en Ciencias - QuímicaDepartamento de QuímicaFacultad de CienciasBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá540 - Química y ciencias afines::543 - Química analíticaNeoplasmasCancerNeoplasmsCáncerpéptidos anticáncerigenosvalidacióncaracterización fisicoquímicaagentes terapéuticosHPLCEspectrometría de masasTherapeutic peptidesvalidationphysicochemical characterizationtherapeutic agentsHPLCMass spectrometryCaracterización fisicoquímica de un péptido polivalente, derivado de la Lactoferricina Bovina, candidato a fármaco para el tratamiento del cáncer de mamaPhysicochemical characterization of a polyvalent peptide, derived from Bovine Lactoferricin, drug candidate for breast cancer treatmentTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionDataPaperhttp://purl.org/redcol/resource_type/TMWHO. 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Technometrics. 1959;1(4):311.Desarrollo 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-clínicosMINCIENCIASEstudiantesInvestigadoresMaestrosPúblico generalLICENSElicense.txtlicense.txttext/plain; charset=utf-84675https://repositorio.unal.edu.co/bitstream/unal/82290/5/license.txtb577153cc0e11f0aeb5fc5005dc82d8aMD55ORIGINALTesis Maestría Kevin Huertas V-Final Repositorio.pdfTesis Maestría Kevin Huertas V-Final Repositorio.pdfTesis de Maestría en Ciencias - Químicaapplication/pdf3991121https://repositorio.unal.edu.co/bitstream/unal/82290/6/Tesis%20Maestr%c3%ada%20Kevin%20Huertas%20V-Final%20Repositorio.pdf8d369f2a8dcec6ecbbe3f16f40bf518bMD56THUMBNAILTesis Maestría Kevin Huertas V-Final Repositorio.pdf.jpgTesis Maestría Kevin Huertas V-Final Repositorio.pdf.jpgGenerated 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