Generic placeholder image

Current Drug Targets

Editor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Applications of Biophysical Tools to Target-Based Discovery of Novel Antibacterial Leads

Author(s): Sushmita Lahiri, Steven Kazmirski, Gunther Kern and Gautam Sanyal

Volume 13, Issue 3, 2012

Page: [388 - 408] Pages: 21

DOI: 10.2174/138945012799424660

Price: $65

Abstract

New antibacterial drugs are urgently needed to combat the growing problem of multidrug resistant bacterial infections. Major advances in bacterial genomics have uncovered many unexploited targets, leading to the possibility of discovering new antibacterials with novel mechanisms that would circumvent resistance. Many of these targets are soluble enzymes that vary in their degrees of mechanistic complexity. Protein crystallography as well as solution based biophysical methods are playing an increasingly important role in selecting, characterizing and validating promising targets as well as identifying and optimizing lead compounds that inhibit their functions. Advances made in recent years in sensitivity, resolution and throughput of biophysical tools are allowing multiple approaches to screening for hits and rational design of leads based on a deeper understanding of structure-activity relationships. However, the path from a lead compound to a safe and efficacious antibacterial drug still remains challenging. Structural and biophysical approaches have had less of an impact on this later phase of discovery than on the lead generation phase.

Keywords: Antibacterial drugs, bacterial targets, biophysical tools, lead generation, target validation, crystal structure, NMR spectroscopy, biophysical approaches, screening, KdsA


Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy