Synthesis and biological activity of a potent optically pure autoinducer-2 quorum sensing agonist

Osvaldo S. Ascenso, Inês M. Torcato, Ana Sofia Miguel, João C. Marques, Karina B. Xavier, M. Rita Ventura, Christopher D. Maycock

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Quorum sensing (QS) regulates population-dependent bacterial behaviours, such as toxin production, biofilm formation and virulence. Autoinducer-2 (AI-2) is to date the only signalling molecule known to foster inter-species bacterial communication across distantly related bacterial species. In this work, the synthesis of pure enantiomers of C4-propoxy-HPD and C4-ethoxy-HPD, known AI-2 analogues, has been developed. The optimised synthesis is efficient, reproducible and short. The (4S) enantiomer of C4-propoxy-HPD was the most active compound being approximately twice as efficient as (4S)-DPD and ten-times more potent than the (4R) enantiomer. Additionally, the specificity of this analogue to bacteria with LuxP receptors makes it a good candidate for clinical applications, because it is not susceptible to scavenging by LsrB-containing bacteria that degrade the natural AI-2. All in all, this study provides a new brief and effective synthesis of isomerically pure analogues for QS modulation that include the most active AI-2 agonist described so far.

Original languageEnglish
Pages (from-to)75-81
Number of pages7
JournalBioorganic Chemistry
Volume85
DOIs
Publication statusPublished - 1 Apr 2019

Keywords

  • AI-2
  • DPD
  • DPD agonists
  • DPD analogues
  • Quorum sensing

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