Synthesis of tritium labelled and photoactivatable N-acyl-L-homoserine lactones - Inter kingdom signalling molecules

  • chair:

    Jakubczyk, D. / Brenner-Weiss, G. / Bräse, S. (2013)
  • place:

    Eur J Org Chem. 3 (2014), 592-597
  • Date: 2014

  • Jakubczyk, D. / Brenner-Weiss, G. / Bräse, S. (2013): „Synthesis of tritium labelled and photoactivatable N-acyl-L-homoserine lactones - Inter kingdom signalling molecules“. In: Eur J Org Chem. 3 (2014), 592-597

Abstract

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N-Acyl-L-homoserine lactones (AHLs) are signal molecules that are synthesized in nature by Gram-negative bacteria. They allow communication between bacteria (quorum sensing) and between microorganisms and their eukaryotic host cells (inter-kingdom signalling). However, very little is known about the mechanisms of the latter system. Therefore, tritium labelled photoactivatable AHLs were synthesized to identify specific receptors in immune cells (e.g., human polymorphonuclear neutrophils, PMN) that bind to AHL. A photoaffinity label – a diazirine group – was chosen as the smallest possible photoactivatable group that can be activated by light irradiation.

The resulting highly active carbene will bind covalently to the closest chemical structure in the pocket of the receptor. The diazirine label was introduced into the AHL molecule according to a literature method. To isolate the labelled receptor from the cellular protein moiety, the AHL was additionally labelled with tritium. During the development of an effective isotopic labelling method, a simple route to hydrogen isotope incorporation into the AHLs was proposed and explored in detail. According to the new protocol, the photoactivatable diazirine-AHL was labelled with deuterium and tritium by a postsynthetic catalytic exchange of the hydrogen with its isotopes, using deuterium or tritium labelled water along with catalytic amounts of metal salts under mild basic conditions.