Publication: Chemical probes for the study of the endogenous cannabinoid system
Loading...
Files
Official URL
Full text at PDC
Publication Date
2016-04-01
Authors
Editors
Journal Title
Journal ISSN
Volume Title
Publisher
Universidad Complutense de Madrid
Citations
Exportar
Abstract
La química biológica nació hace dos décadas con objeto de estudiar la interfase entre la química y la biología, utilizando para ello herramientas capaces de interrogar los distintos sistemas biológicos, facilitando así la comprensión de los mismos.1-3 Sin embargo, existen sistemas biológicos de gran relevancia cuyo estudio no ha sido abordado hasta ahora. Uno de ellos es el sistema cannabinoide endógeno (endogenous cannabinoid system, ECS), que durante los últimos años ha sido relacionado con diversas funciones fisiológicas a nivel tanto central como periférico.4-7 Sin embargo, no existe ningún fármaco en el mercado a día de hoy dirigido a la modulación de este sistema. En este contexto, una mayor comprensión de algunos de los aspectos de la biología del ECS, tales como la localización de los receptores de cannabinoides (cannabinoid receptors, CBRs) a nivel celular, su localización a nivel subcelular, la existencia de otras dianas distintas de los receptores conocidos y molecularmente caracterizados CB1R y CB2R, y el estudio de otros ligandos de los CBRs, podrían permitir una aplicación terapéutica real de este sistema. Así, los objetivos generales del presente trabajo de investigación son: i) el desarrollo de sondas para el estudio de la expresión de los CBRs en el sistema inmune, ii) el diseño y síntesis de herramientas para explorar las diferencias entre el CB1R de la membrana plasmática y el mitocondrial, iii) el descubrimiento de las dianas adicionales de los agonistas sintéticos HU210 y HU308, y iv) la identificación de las dianas terapéuticas del producto de origen natural honokiol...
Chemical biology emerged two decades ago aimed at the study of the interface between chemistry and biology, producing a great improvement in our understanding of complex biological systems by means of the development of chemical tools able to interrogate them.1-3 In spite of these advances, there are relevant systems that hold great therapeutic promise but which have not been studied up to date. One of these cases is the endogenous cannabinoid system (ECS), which has been involved in almost every central and peripheral function.4-7 However, there is no drug in the market targeting this system so far. In this context, it seems clear that there is a crucial need to understand some aspects of the biology of the ECS in a deeper manner. Among them, the cellular location of cannabinoid receptors (CBRs), as well as their localization within the cell, the existence of other cannabinoid targets different from the molecularly characterized CB1R and CB2R, and the study of interesting cannabinoid-related ligands, might help to exploit the therapeutic potential of the ECS. Thus, the overall objectives for the present work are: i) the development of probes to study the expression of CBRs in the immune system, ii) the design and synthesis of tools to explore the differences between plasma and mitochondrial CB1Rs, iii) the discovery of the off-targets of the synthetic CBR agonists HU210 and HU308, and iv) the identification of the binding proteins of the natural product honokiol...
Chemical biology emerged two decades ago aimed at the study of the interface between chemistry and biology, producing a great improvement in our understanding of complex biological systems by means of the development of chemical tools able to interrogate them.1-3 In spite of these advances, there are relevant systems that hold great therapeutic promise but which have not been studied up to date. One of these cases is the endogenous cannabinoid system (ECS), which has been involved in almost every central and peripheral function.4-7 However, there is no drug in the market targeting this system so far. In this context, it seems clear that there is a crucial need to understand some aspects of the biology of the ECS in a deeper manner. Among them, the cellular location of cannabinoid receptors (CBRs), as well as their localization within the cell, the existence of other cannabinoid targets different from the molecularly characterized CB1R and CB2R, and the study of interesting cannabinoid-related ligands, might help to exploit the therapeutic potential of the ECS. Thus, the overall objectives for the present work are: i) the development of probes to study the expression of CBRs in the immune system, ii) the design and synthesis of tools to explore the differences between plasma and mitochondrial CB1Rs, iii) the discovery of the off-targets of the synthetic CBR agonists HU210 and HU308, and iv) the identification of the binding proteins of the natural product honokiol...
Description
Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Químicas, Departamento de Química Orgánica I, leída el 27-10-2015