Tailor-made LasR agonists modulate quorum sensing in Pseudomonas aeruginosa

Nira Rabin, Antonia Delago, Boaz Inbal, Pnina Krief, Michael M. Meijler

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

The primary quorum sensing system in the opportunistic pathogen Pseudomonas aeruginosa is regulated through the synthesis and secretion of N-3-oxo-dodecanoyl-l-homoserine lactone (C12) which binds the transcriptional activator LasR. In this study we report the design, synthesis and biological evaluation of new analogs of C12. Analysis of the autoinducer binding site cavity of LasR revealed a positively charged cavity near the center of bound C12. Accordingly, we synthesized two piperidine-C12 diastereoisomers and tested their biological activity. Both analogs proved to be strong LasR agonists that showed a synergistic effect when presented together with the natural ligand. Moreover, binding of the analogs resulted in phenotypic changes characteristic of QS controlled receptor activation.

Original languageEnglish
Pages (from-to)7155-7163
Number of pages9
JournalOrganic and Biomolecular Chemistry
Volume11
Issue number41
DOIs
StatePublished - 7 Nov 2013

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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