4 research outputs found
Hydrophobic waters in bromodomains
Targeting epigenetic proteins is a rapidly growing area for medicinal chemistry and drug discovery. Recent years have seen an explosion of interest in developing small molecules binding to bromodomains due to their implication in cancer, inflammation, and a plethora of diseases. Several small-molecule inhibitors and degraders that target bromodomains have entered the clinic, and many more are increasingly being used as chemical probes to describe bromodomain biology. From a structural point of view, crystallographic studies of bromodomains describe, as a common feature, five water molecules as an integral part of the acetyl-lysine binding pocket. These water molecules are essential in druggability and are described as a functional part of the protein [1,2]. In this framework, we focused our attention on the description of the hydrophilic/hydrophobic character of these molecules, which seem to create a favorable environment for the recognition of hydrophobic groups. To this end, and following fragment-based drug design techniques, here we describe a new family of small molecules with a 5-phenylthiazolo[2,3-c][1,2,4]triazol nucleus and probe the water site with various substituents at the 3-position endowing hydrophilic or hydrophobic properties. In this work, we present the theoretical calculations, the synthesis of the new compounds, the results of differential scanning fluorimetry (DSF) and isothermal titration calorimetry (ITC), and the crystal structures of three of our compounds with the target protein. The study sheds light on the counterintuitive behavior of the water molecules in this particular environment
Fibrosi quÃstica. Coneixements i paper del farmacèutic
Treballs d'Educació Farmacètica als ciutadans. Unitat Docent d'Estades en Prà ctiques Tutelades. Facultat de Farmà cia, Universitat de Barcelona. Curs: 2014/2015, Tutors: Anna Mas Comas i Marian March Pujol.La Fibrosi QuÃstica és una malaltia heredità ria que es desenvolupa des del
naixement i afecta a la majoria dels òrgans, sent el pà ncrees i els pulmons els
més perjudicats. En els últims anys la supervivència dels pacients amb FQ ha
augmentat degut a que es disposa de més fà rmacs i més efectius pel seu
tractament. Tot i aixÃ, el tractament d’aquesta malaltia es molt complex, raó per
la qual el pacient ha de disposar de la informació necessà ria per al bon
compliment d’aquest. Amb la realització d’aquest treball s’ha intentat informar
als pacients i familiars sobre la malaltia, donar les eines necessà ries per
aprofitar al mà xim el seu tractament i exemplificar com els farmacèutics, com a
professionals sanitaris, poden ajudar als pacients en aquesta tasca
Drugging the Fbw7 E3 Ligase with a Fragment-Based Approach
Fbw7 is an important E3 ligase and one of the most commonly deregulated proteins in human cancers. [...