Focus on the controversial activation of human iNKT cells by 4-deoxy analogue of KRN7000

  • J Med Chem. 2009 Aug 13;52(15):4960-3. doi: 10.1021/jm900290r.
Vivien Lacône  1 ,  Julie Hunault ,  Muriel Pipelier ,  Virginie Blot ,  Thomas Lecourt ,  Jézabelle Rocher ,  Anne-Laure Turcot-Dubois ,  Séverine Marionneau ,  Jean-Yves Douillard ,  Monique Clément ,  Jacques Le Pendu ,  Marc Bonneville ,  Laurent Micouin ,  Didier Dubreuil
Affiliations
  • 1. Université de Nantes, CNRS, Chimie et Interdisciplinarité: Synthèse, Analyse, Modélisation (CEISAM), UMR CNRS 6230, Faculté des Sciences et des Techniques, 2 Rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
PMID: 19580320 DOI: 10.1021/jm900290r
Abstract

4-Deoxy-alpha-GalCer analogues are considered weaker agonists than KRN7000 for the stimulation of human iNKT cells, but this remains strongly debated. In this work, we described a strategy toward 4-deoxy-alpha-GalCers with, as a key step, a metathesis reaction allowing sphingosine modifications from a single ethylenic alpha-galactoside precursor. The 4-deoxy-KRN7000 derivative 2, described here, induced potent cytokinic responses, comparable to those of KRN7000, both from human iNKT cells in vitro and from their murine counterpart in vivo.