Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Probing autoinducer-2 based quorum sensing: The biological consequences of molecules unable to traverse equilibrium states

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Tsuchikama, K.
  • Lowery, Colin
  • Janda, Kim

publication date

  • September 2011

journal

  • Journal of Organic Chemistry  Journal

abstract

  • Bacteria have developed a cell-to-cell communication system, termed quorum sensing (QS), which allows for the population-dependent coordination of their behavior via the exchange of chemical signals. Autoinducer-2 (AI-2), a class of QS signals derived from 4,5-dihydroxy-2,3-pentandione (DPD), has been revealed as a universal signaling molecule in a variety of bacterial species. In spite of considerable interest, the study of putative AI-2 based QS systems remains a challenging topic in part due to the rapid interconversion between the linear and cyclic forms of DPD. Herein, we report the design and development of efficient syntheses of carbocyclic analogues of DPD, which are locked in the cyclic form. The synthetic analogues were evaluated for the modulation of AI-2-based QS in Vibrio harveyi and Salmonella typhimurium. No agonists were uncovered in either V. harveyi or S. typhimurium assay, whereas weak to moderate antagonists were found against V. harveyi. On the basis of NMR analyses and DFT calculations, the heterocyclic oxygen atom within DPD appears necessary to promote hydration at the C3 position of cyclic DPD to afford the active tetrahydroxy species. These results also shed light on the interaction between the heterocyclic oxygen atom and receptor proteins as well as the importance of the linear form and dynamic equilibrium of DPD as crucial requirements for activation of AI-2 based QS circuits.

subject areas

  • Homoserine
  • Lactones
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Pentanones
  • Quantum Theory
  • Quorum Sensing
  • Salmonella typhimurium
  • Vibrio
scroll to property group menus

Identity

PubMed Central ID

  • PMC3162994

International Standard Serial Number (ISSN)

  • 0022-3263

Digital Object Identifier (DOI)

  • 10.1021/jo200882k

PubMed ID

  • 21678949
scroll to property group menus

Additional Document Info

start page

  • 6981

end page

  • 6989

volume

  • 76

issue

  • 17

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support