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

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

Volume: 13 Issue: 3

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

Affiliation:

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

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.

Cite this article as:

Lahiri Sushmita, Kazmirski Steven, Kern Gunther and Sanyal Gautam, Applications of Biophysical Tools to Target-Based Discovery of Novel Antibacterial Leads, Current Drug Targets 2012; 13 (3) . https://dx.doi.org/10.2174/138945012799424660