Binding evaluation of fragment-based scaffolds for probing allosteric enzymes - Archive ouverte HAL Access content directly
Journal Articles Journal of Medicinal Chemistry Year : 2012

Binding evaluation of fragment-based scaffolds for probing allosteric enzymes

Abstract

Fragment-based drug discovery has become a powerful method for the generation of drug leads against therapeutic targets. Beyond the identification of novel and effective starting points for drug design, fragments have emerged as reliable tools for assessing protein druggability and identifying protein hot spots. Here, we have examined fragments resulting from the deconstruction of known inhibitors from the glycogen phosphorylase enzyme, a therapeutic target against type 2 diabetes, with two motivations. First, we have analyzed the fragment binding to the multiple binding sites of the glycogen phosphorylase, and then we have investigated the use of fragments to study allosteric enzymes. The work we report illustrates the power of fragmentlike ligands not only for probing the various binding pockets of proteins, but also for uncovering cooperativity between these various binding sites.
Not file

Dates and versions

hal-01087963 , version 1 (27-11-2014)

Identifiers

Cite

Isabelle Krimm, Jean-Marc Lancelin, Jean-Pierre Praly. Binding evaluation of fragment-based scaffolds for probing allosteric enzymes. Journal of Medicinal Chemistry, 2012, 55 (3), pp.1287-1295. ⟨10.1021/jm201439b⟩. ⟨hal-01087963⟩
117 View
0 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More