Fragment-Based Lead Discovery Strategies in Antimicrobial Drug Discovery

Monika I Konaklieva; Balbina J Plotkin

doi:10.3390/antibiotics12020315

Fragment-Based Lead Discovery Strategies in Antimicrobial Drug Discovery

Antibiotics (Basel). 2023 Feb 3;12(2):315. doi: 10.3390/antibiotics12020315.

Authors

Monika I Konaklieva¹, Balbina J Plotkin²

Affiliations

¹ Department of Chemistry, American University, Washington, DC 20016, USA.
² Department of Microbiology and Immunology, Midwestern University, Downers Grove, IL 60515, USA.

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 (K_D ~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; STD NMR; antimicrobial; inhibitors of pathogenic bacterial enzymes; multidrug resistance; phenotypic screens.

Publication types

Review

Grants and funding

This research received no external funding.