New Approaches in Sensing and Targeting Bacterial rRNA A-site

Med Chem. 2021;17(4):299-309. doi: 10.2174/1573406415666191011160035.

Abstract

New chemical agents that could combat increasing antibiotic resistance are urgently needed. In this mini-review, an old but highly relevant RNA sequence which is crucial for the continuation of bacterial life-cycle is covered. Some of the most significant advances of the last decade in sensing and targeting the bacterial rRNA A-site: a well-validated binding site of proverbially known aminoglycoside antibiotics are described. Some of the major advances in direct sensing of the bacterial decoding side (A-site) are described and also new fluorescent molecules that are capable of detecting lead compounds through high-throughput assays by displacement of fluorescent probe molecules are highlighted. Lastly, some of the recently discovered non-aminoglycoside small molecule binders of bacterial rRNA A-site as a new class of molecules that could provide future scaffolds and molecules for developing new antibacterial agents have been discussed.

Keywords: A-site; FRET; Mycobacterium tuberculosis; antimicrobial agents; drug discovery; rRNA.

Publication types

  • Review

MeSH terms

  • Aminoglycosides / chemical synthesis
  • Aminoglycosides / metabolism
  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / metabolism*
  • Bacteria / chemistry
  • Bacteria / drug effects
  • Binding Sites
  • Fluorescent Dyes / chemistry
  • Naphthyridines / metabolism
  • Peptide Nucleic Acids / metabolism
  • RNA, Bacterial / metabolism*
  • RNA, Ribosomal / metabolism*
  • Spiro Compounds / metabolism

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Fluorescent Dyes
  • Naphthyridines
  • Peptide Nucleic Acids
  • RNA, Bacterial
  • RNA, Ribosomal
  • Spiro Compounds