Quimiogenómica y Quimiogenética: Definiciones, técnicas y aplicaciones en el ámbito farmacéutico
Barra lateral del artículo
Publicado:
feb. 27, 2020
Palabras clave:
Biotecnología, Quimiogenética, Quimiogenómica, Farmacia, DREADDs
Contenido principal del artículo
Resumen
En los años 80, tomó fuerza la ciencia dirigida al estudio del genoma humano, cuyo objetivo era mejorar la salud humana a través de la identificación de genes. Este estudio permitió el surgimiento de ciencias, entre ellas la Quimiogenómica y la Quimiogenética. La Quimiogenómica es un área interdisciplinaria que busca la sistematización del genoma al identificar, analizar, expandir y predecir las interacciones de los ligandos con las proteínas por medio de métodos in vitro e in silico. Por otro lado, la Quimiogenética se refiere al estudio de las características genéticas de un paciente para optimizar la Farmacoterapia y predecir la eficacia, los efectos secundarios y la dosificación de fármacos selectos. El conocimiento de las interacciones entre moléculas y proteínas específicas ayudaron al desarrollo de nuevas herramientas biotecnológicas y a la identificación de novedosas dianas farmacológicas que pudieran conducir a conocimientos más específicos. Algunas aplicaciones en estudio en el ámbito farmacéutico son los receptores diseñados exclusivamente activados por fármacos diseñados (DREADDs, por sus siglas en inglés). Con ellos se pretende que no se activen ante ligandos endógenos, sino en presencia de sintéticos. Actualmente existen muchas investigaciones en los cuales se estudian DREADDs para la identificación de neuronas y de vías de señalización involucradas en patologías como el miedo, la ansiedad, la depresión, la adicción y la obesidad.
Detalles del artículo
Cómo citar
Quimiogenómica y Quimiogenética: Definiciones, técnicas y aplicaciones en el ámbito farmacéutico. (2020). Revista Tecnología En Marcha, 33(1), Pág. 3–16. https://doi.org/10.18845/tm.v33i1.5017
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Artículo científico
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Citas
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[53] T. J. Ahonen, M. Rinne, P. Grutschreiber, K. Mätlik, M. Airavaara, D. Schaarschmidt et al, “Synthesis of 7ß-hydroxy-8-ketone opioid derivatives with antagonist activity at mu- and delta-opioid receptors,” European Journal of Medicinal Chemistry, 151, 495-507, 2018.
[54] P. Kunz, T. Flock, N. Soler, M. Zaiss, C. Vincke, Y. Sterckx et al, “Exploiting sequence and stability information for directing nanobody stability engineering,” Biochimica et Biophysica Acta - General Subjects, 1861(9), 2196-2205, 2017.
[55] M. R. Bruchas and B. L. Roth, “New Technologies for Elucidating Opioid Receptor Function,” Trends in Pharmacological Sciences, 37(4), 279-289, 2016.
[56] E. Vardy, J. E. Robinson, C. Li, R. H. J. Olsen, J. F. DiBerto, P. M. Giguere et al, “A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior,” Neuron, 86(4), 936-946, 2015.
[2] J. L. Jameson and P. Kopp, “Principios de genética humana,” en Harrison. Principios de Medicina Interna, 19 ed., D. Kasper, A. Fauci, S. Hauser, D. Longo, J. L. Jameson, and J. Loscalzo, Ed. Nueva York: Mc Graw Hill Medical, 2016.
[3] I. Silva Zolezzi, “Genómica y medicina,” Educación Química, 22(1), 15-27, 2011.
[4] F. S. Collins, M. Morgan, and A. Patrinos, “The Human Genome Project: Lessons from Large-Scale Biology,” Science, 300(5617), 286-290, 2003.
[5] E. S. Lander, L. M. Linton, B. Birren, C. Nusbaum, M. C. Zody, J. Baldwin et al, “Initial sequencing and analysis of the human genome,” Nature, 409(6822), 860-921, 2001.
[6] J. C. Venter, M. D. Adams, E. W. Myers, P. W. Li, R. J. Mural, G. G. Sutton et al, “The sequence of the human genome,” Science, 291(5507), 1304-1351, 2001.
[7] E. Barreto-Hernández and M. T. Reguero Reza, “Grupo de Bioinformática: En la frontera del análisis de datos moleculares,” Revista Colombiana de Biotecnología, 2017: Conmemoración IBUN 30 años, 23-26, 2017.
[8] S. Wu-Pong and R. Shiang, “The Use of Bioinformatics and Chemogenomics in Drug Discovery,” in Biopharmaceutical Drug Design and Development, 2 ed., S. Wu-Pong and Y. Rojanasakul, Ed. Berlin: Springer, 2008, pp. 31-45.
[9] A. Jara y J. J. Kopchick, “Proteómica: una aproximación integral,” Anales de Pediatría, 78(3), 137-139, 2013.
[10] M. Tyers and M. Mann, “From genomics to proteomics,” Nature, 422(6928), 193-197, 2003.
[11] S. M. Sternson and B. L. Roth, “Chemogenetic Tools to Interrogate Brain Functions,” Annual Review of Neuroscience, 37, 387-407, 2014.
[12] E. Jacoby, Computational Chemogenomics, New Western United States: Taylor & Francis Group, 2013.
[13] L. Delgado-Soler y J. Rubio Martínez, “Quimiogenómica: una nueva aproximación al diseño de fármacos,” Farmespaña Industrial, 32, 73-75, 2009.
[14] C. J. Harris and A. P. Stevens, “Chemogenomics: structuring the drug discovery process to gene families,” Drug Discovery Today, 11(19-20), 880-888, 2006.
[15] D. Gupta-Ostermann and J. Bajorath, “The ´Sar Matrix´ method and its extensions for applications in medicinal chemistry and chemogenomics (version 2),” F1000 Research, 3(113), 2014.
[16] S. Ahn, A. W. Kahsai, B. Pani, Q. T. Wang, S. Zhao, A. L. Wall et al, “Allosteric “beta-blocker” isolated from a DNA-encoded small molecule library,” Proceedings of the National Academy of Sciences of the United States of America, 114(7), 1708-1713, 2017.
[17] J. L. Medina-Franco, E. Fernández-de Gortari y J. J. Navaja, “Avances en el diseño de fármacos asistido por computadora,” Educación Química, 26(3), 180-186, 2015.
[18] M. Bredel and E. Jacoby, “Chemogenomics: an emerging strategy for rapid target and drug discovery,” Nature Reviews Genetics, 5(4), 262-275, 2004.
[19] L. H. Jones and M. E. Bunnage, “Applications of chemogenomic library screening in drug discovery,” Nature Reviews Drug Discovery, 16(4), 285-296, 2017.
[20] A. Cereto-Massagué, M. J. Ojeda, C. Valls, M. Mulero, G. Pujadas, and S. Garcia-Vallve, “Tools for in silico target fishing,” Methods, 71, 98-103, 2015.
[21] H. Pérez-Sánchez, G. Cano, J. García-Rodríguez y J. M. Cecilia, “Descubrimiento de fármacos basado en cribado virtual refinado con enfoques neuronales paralelos,” Revista Internacional de Métodos Numéricos para Cálculo y Diseño en Ingeniería, 31(4), 207-211, 2015.
[22] D. J. Urban and B. L. Roth, “DREADDs (Designer Receptors Exclusively Activated by Designer Drugs): Chemogenetic Tools with Therapeutic Utility,” Annual Review of Pharmacology and Toxicology, 55, 399-417, 2015.
[23] K. S. Smith, D. J. Bucci, B. W. Luikart, and S. V. Mahler, “DREADDS: Use and application in behavioral neuroscience,” Behavioral Neuroscience, 130(2), 137-155, 2016.
[24] E. J. Campbell and N. J. Marchant, “The use of chemogenetics in behavioural neuroscience: receptor variants, targeting approaches and caveats,” British Journal of Pharmacology, 175(7), 994-1003, 2018.
[25] F. Saldívar-González, F. D. Prieto-Martínez y J. L. Medina-Franco, “Descubrimiento y desarrollo de fármacos: un enfoque computacional,” Educación Química, 28(1), 51-58, 2017.
[26] T. I. Ramos, “Contexto actual de los estudios preclínicos,” Bionatura, 1(3), 103-105, 2016.
[27] P. McGonigle and B. Ruggeri, “Animal models of human disease: Challenges in enabling translation,” Biochemical Pharmacology, 87(1), 162-171, 2014.
[28] A. Wuster and M. Madan Babu, “Chemogenomics and biotechnology,” Trends in Biotechnology, 26(5), 252-258, 2008.
[29] D. E. Gloriam, “Chemogenomics of allosteric binding sites in GPCRs,” Drug Discovery Today: Technologies, 10(2), e307-e313, 2013.
[30] B. Pirard, “Structure-Based Chemogenomics: Analysis of Protein Family Landscapes,” Methods in Molecular Biology, 575, 281-296, 2009.
[31] Z. Gao, S. Rohani, J. Gong, and J. Wang, “Recent Developments in the Crystallization Process: Toward the Pharmaceutical Industry,” Engineering, 3(3), 343-353, 2017.
[32] T. T. Ashburn and K. B. Thor, “Drug repositioning: identifying and developing new uses for existing drugs,” Nature Reviews Drug Discovery, 3(8), 673-683, 2004.
[33] M. Bieler, R. Heilker, H. Köppen, and G. Schneider, “Assay Related Target Similarity (ARTS) - Chemogenomics Approach for Quantitative Comparison of Biological Targets,” Journal of Chemical Information and Modeling, 51(8), 1897-1905, 2011.
[34] B. E. Evans, K. E. Rittle, M. G. Bock, R. M. DiPardo, R. M. Freidinger, W. L. Whitter et al, “Methods for Drug Discovery: Development of Potent, Selective, Orally Effective Cholecystokinin Antagonists,” Journal of Medicinal Chemistry, 31(12), 2235-2246, 1988.
[35] H. M. Lee, P. M. Giguere, and B. L. Roth, “DREADDs: novel tools for drug discovery and development,” Drug Discovery Today, 19(4), 469-473, 2014.
[36] J. A. Allen and B. L. Roth, “Strategies to Discover Unexpected Targets for Drugs Active at G Protein-Coupled Receptors, Annual Review of Pharmacology and Toxicology, 51, 117-144, 2011.
[37] B. L. Roth, “DREADDs for Neuroscientists,” Neuron, 89(4), 683-694, 2016.
[38] B. Hall, A. Limaye, and A. B. Kulkarni, “Overview: Generation of Gene Knockout Mice,” Current Protocols in Cell Biology, 44(1), 19.12.1-19.12.17, 2009.
[39] B. N. Armbruster, X. Li, M. H. Pausch, S. Herlitze, and B. L. Roth, “Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand,” Proceedings of the National Academy of Sciences of the United States of America, 104(12), 5163-5168, 2007.
[40] S. J. Bradley, A. B. Tobin, and R. Prihandoko, “The use of chemogenetic approaches to study the physiological roles of muscarinic acetylcholine receptors in the central nervous system,” Neuropharmacology, 136(Part C), 421-426, 2018.
[41] J. M. Guettier, D. Gautam, M. Scarselli, I. Ruiz de Azua, J. H. Li, E. Rosemond et al, “A chemical-genetic approach to study G protein regulation of ß cell function in vivo,” Proceedings of the National Academy of Sciences of the United States of America, 106(45), 19197-19202, 2009.
[42] J. L. Gomez, J. Bonaventura, W. Lesniak, W. B. Mathews, P. Sysa-Shah, L. A. Rodriguez et al, “Chemogenetics revealed: DREADD occupancy and activation via converted clozapine,” Science, 357(6350), 503-507, 2017.
[43] Y. Pei, S. Dong, and B. L. Roth, “Generation of Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) Using Directed Molecular Evolution,” Current Protocols in Neuroscience, 50(1), 4.33.1-4.33.25, 2010.
[44] D. S. Wilson and A. D. Keefe, “Random mutagenesis by PCR,” Current Protocols in Molecular Biology, 51(1), 8.3.1-8.3.9, 2000.
[45] V. Nawaratne, K. Leach, N. Suratman, R. E. Loiacono, C. C. Felder, B. N. Armbruster et al, “New Insights into the Function of M4 Muscarinic Acetylcholine Receptors Gained Using a Novel Allosteric Modulator and a DREADD (Designer Receptor Exclusively Activated by a Designer Drug),” Molecular Pharmacology, 74(4), 1119-1131, 2008.
[46] C. Lüscher and P. A. Slesinger, “Emerging roles for G protein-gated inwardly rectifying potassium (GIRK) channels in health and disease,” Nature Reviews Neuroscience, 11(5), 301-315, 2010.
[47] M. E. Tipps and K. J. Buck, “Girk Channels: A Potential Link Between Learning and Addiction,” 123, 239-277, 2015.
[48] D. Atasoy, J. N. Betley, H. H. Su, and S. M. Sternson, “Deconstruction of a neural circuit for hunger,” Nature, 488(7410), 172-177, 2012.
[49] B. R. Conklin, E. C. Hsiao, S. Claeysen, A. Dumuis, S. Srinivasan, J. R. Forsayeth et al, “Engineering GPCR signaling pathways with RASSLs,” Nature Methods, 5(8), 673-678, 2008.
[50] G. M. Alexander, S. C. Rogan, A. I. Abbas, B. N. Armbruster, Y. Pei, J. A. Allen et al, “Remote Control of Neuronal Activity in Transgenic Mice Expressing Evolved G protein-couple receptors,” Neuron, 63(1), 27-39, 2009.
[51] C. Agulhon, K. M. Boyt, A. X. Xie, F. Friocourt, B. L. Roth, and K. D. McCarthy, “Modulation of the autonomic nervous system and behaviour by acute glial cell Gq protein-coupled receptor activation in vivo,” The Journal of Physiology, 591(22), 5599-5609, 2013.
[52] M. S. Farrell and B. L. Roth, “Pharmacosynthetics: Reimagining the pharmacogenetic approach,” Brain Research, 1511, 6-20, 2013.
[53] T. J. Ahonen, M. Rinne, P. Grutschreiber, K. Mätlik, M. Airavaara, D. Schaarschmidt et al, “Synthesis of 7ß-hydroxy-8-ketone opioid derivatives with antagonist activity at mu- and delta-opioid receptors,” European Journal of Medicinal Chemistry, 151, 495-507, 2018.
[54] P. Kunz, T. Flock, N. Soler, M. Zaiss, C. Vincke, Y. Sterckx et al, “Exploiting sequence and stability information for directing nanobody stability engineering,” Biochimica et Biophysica Acta - General Subjects, 1861(9), 2196-2205, 2017.
[55] M. R. Bruchas and B. L. Roth, “New Technologies for Elucidating Opioid Receptor Function,” Trends in Pharmacological Sciences, 37(4), 279-289, 2016.
[56] E. Vardy, J. E. Robinson, C. Li, R. H. J. Olsen, J. F. DiBerto, P. M. Giguere et al, “A New DREADD Facilitates the Multiplexed Chemogenetic Interrogation of Behavior,” Neuron, 86(4), 936-946, 2015.