Identification of lead compounds as antagonists of protein Bcl-xL with a diversity-oriented multidisciplinary approach.
We report on the use of a diversity oriented synthesis (DOS) approach that resulted in the generation of a set of libraries of compounds presenting novel structural cores. These chemical cores have been employed to design potential antagonists of the antiapoptotic protein Bcl-x(L) through reiterated steps of molecular docking calculations followed by experimental verification of binding. Our data suggest that the DOS approach is suitable to generate novel scaffolds, which can be employed to target protein-protein interactions.
Dipartimento di Scienze Farmaceutiche, Universita degli studi di Salerno, Via Ponte don Melillo, 84084 Fisciano, SA, Italy.
Simone
S
Di Micco
Romina
R
Vitale
Maurizio
M
Pellecchia
Michele F
MF
Rega
Renata
R
Riva
Andrea
A
Basso
Giuseppe
G
Bifulco
D055808:Drug Discovery / Q000379:methods*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D051020:bcl-X Protein / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D054852:Small Molecule Libraries; D051020:bcl-X Protein