Novel paromamine derivatives exploring shallow-groove recognition of ribosomal-decoding-site RNA

Chembiochem. 2002 Dec 2;3(12):1223-8. doi: 10.1002/1439-7633(20021202)3:12<1223::AID-CBIC1223>3.0.CO;2-W.

Abstract

Natural aminoglycoside antibiotics recognize an internal loop of bacterial ribosomal-decoding-site RNA by binding to the deep groove of the RNA structure. We have designed, synthesized, and tested RNA-targeted paromamine derivatives that exploit additional interactions on the shallow groove face of the decoding-site RNA. An in vitro transcription-translation assay of a series of 6'-derivatives showed the 6'-position to be very sensitive to substitution. This result suggests that the group at the 6'-position plays a pivotal role in RNA target recognition.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aminoglycosides / chemical synthesis*
  • Aminoglycosides / chemistry
  • Aminoglycosides / pharmacology*
  • Anti-Bacterial Agents / chemistry
  • Binding Sites
  • Cell-Free System
  • Drug Design
  • Protein Biosynthesis / drug effects
  • RNA, Bacterial / antagonists & inhibitors
  • RNA, Ribosomal / antagonists & inhibitors*
  • RNA, Ribosomal / chemistry
  • RNA, Ribosomal / ultrastructure
  • Structure-Activity Relationship

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • RNA, Bacterial
  • RNA, Ribosomal
  • paromamine