Towards Dynamic Drug Design: Identification and Optimization of β-Galactosidase Inhibitors from a Dynamic Hemithioacetal System

✍ Scribed by Rémi Caraballo; Morakot Sakulsombat; Olof Ramström

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 314 KB
• Volume: 11
• Category: Article
• ISSN: 1439-4227
• DOI: 10.1002/cbic.201000158

✦ Synopsis

Abstract

A discovery strategy relying on the identification of fragments through resolution of a constitutional dynamic system, coupled to subsequent static ligand design and optimization, is demonstrated. The strategic design and synthesis of the best molecular fragments identified from a dynamic hemithioacetal system into static ligand structures yielded a range of β‐galactosidase inhibitors. Two series of structures mimicking the hemithioacetal motif were envisaged: thioglycosides and C‐glycosides. Inhibition studies provided important structural information for the two groups, and 1‐thiobenzyl‐β‐D‐galactopyranoside demonstrated the best inhibitory effects.