Fragment-Based Lead Discovery Strategies in Antimicrobial Drug Discovery

Abstract

Fragment-based lead discovery (FBLD) is a powerful application for developing ligands as modulators of disease targets. This approach strategy involves identification of interactions between low-molecular weight compounds (100–300 Da) and their putative targets, often with low affinity (KD ~0.1–1 mM) interactions. The focus of this screening methodology is to optimize and streamline identification of fragments with higher ligand efficiency (LE) than typical high-throughput screening. The focus of this review is on the last half decade of fragment-based drug discovery strategies that have been used for antimicrobial drug discovery.

Keywords

• FBLD
• antimicrobial
• multidrug resistance
• inhibitors of pathogenic bacterial enzymes
• phenotypic screens
• STD NMR