Geminal dihalogen isosteric replacement in hydrated AI-2 affords potent quorum sensing modulators

Chem Commun (Camb). 2015 Feb 14;51(13):2617-20. doi: 10.1039/c4cc09361e.

Abstract

Hydrated carbonyl groups in AI-2, a quorum sensing autoinducer, make key hydrogen bonding interactions in the binding site of LsrR (a transcriptional regulator). This can be recapitulated with geminal dibromides, via halogen bonding. Geminal dihalogens represent interesting isosteric replacements for hydrated carbonyls in ligands and are currently under-utilized in ligand design.

Publication types

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

MeSH terms

  • Binding Sites
  • Escherichia coli Proteins / metabolism
  • Homoserine / analogs & derivatives*
  • Homoserine / chemistry
  • Homoserine / metabolism
  • Hydrogen Bonding
  • Lactones / chemistry*
  • Lactones / metabolism*
  • Ligands
  • Models, Molecular
  • Molecular Conformation
  • Quorum Sensing*
  • Repressor Proteins / metabolism
  • Water / chemistry

Substances

  • Escherichia coli Proteins
  • Lactones
  • Ligands
  • LsrR protein, E coli
  • N-octanoylhomoserine lactone
  • Repressor Proteins
  • Water
  • Homoserine