Synthesis of LuxS inhibitors targeting bacterial cell-cell communication

Org Lett. 2004 Sep 2;6(18):3043-6. doi: 10.1021/ol049182i.

Abstract

[reaction: see text] Quorum sensing is a process by which bacteria sense cell density. This cell-cell communication process is mediated by autoinducers. A cross-species messenger, autoinducer-2 (AI-2) is produced from S-ribosyl-L-homocysteine by the LuxS enzyme. A proposed mechanism for LuxS is an aldose-ketose isomerization of S-ribosylhomocysteine followed by a beta-elimination. We report here the synthesis of two substrate analogues, S-anhydroribosyl-L-homocysteine and S-homoribosyl-L-cysteine, which prevent the initial and final step of the mechanism, respectively.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bacteria / drug effects
  • Bacteria / enzymology*
  • Bacteria / metabolism
  • Bacterial Proteins / antagonists & inhibitors*
  • Carbon-Sulfur Lyases
  • Homocysteine / analogs & derivatives*
  • Homocysteine / chemical synthesis*
  • Homocysteine / pharmacology
  • Stereoisomerism
  • Substrate Specificity

Substances

  • Bacterial Proteins
  • S-ribosyl-L-homocysteine
  • Homocysteine
  • Carbon-Sulfur Lyases
  • LuxS protein, Bacteria