Synthesis and biological activity of α-glucosyl C24: 0 and C20:2 ceramides

Peter J. Jervis, Natacha Veerapen, Gabriel Bricard, Liam R. Cox, Steven A. Porcelli, Gurdyal S. Besra

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

α-Glucosyl ceramides 4 and 5 have been synthesised and evaluated for their ability to stimulate the activation and expansion of human iNKT cells. The key challenge in the synthesis of both target molecules was the stereoselective synthesis of the α-glycosidic linkage. Of the methods examined, glycosylation using per-TMS-protected glucosyl iodide 16 was completely α-selective and provided gram quantities of amine 11, from which α-glucosyl ceramides 4 and 5 were obtained by N-acylation. α-GlcCer 4, containing a C24 saturated acyl chain, stimulated a marked proliferation and expansion of human circulating iNKT cells in short-term cultures. α-GlcCer 5, which contains a C20 11,14-cis-diene acyl chain (C20:2), induced extremely similar levels of iNKT cell activation and expansion.

Original languageEnglish (US)
Pages (from-to)3475-3478
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number12
DOIs
StatePublished - 2010

Fingerprint

Natural Killer T-Cells
Ceramides
Bioactivity
Glucosylceramides
Chemical activation
Glycosylation
Acylation
Iodides
Amines
Molecules

Keywords

  • Antigen
  • CD1d
  • Ceramide
  • iNKT
  • Lipid

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Synthesis and biological activity of α-glucosyl C24 : 0 and C20:2 ceramides. / Jervis, Peter J.; Veerapen, Natacha; Bricard, Gabriel; Cox, Liam R.; Porcelli, Steven A.; Besra, Gurdyal S.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 20, No. 12, 2010, p. 3475-3478.

Research output: Contribution to journalArticle

Jervis, Peter J. ; Veerapen, Natacha ; Bricard, Gabriel ; Cox, Liam R. ; Porcelli, Steven A. ; Besra, Gurdyal S. / Synthesis and biological activity of α-glucosyl C24 : 0 and C20:2 ceramides. In: Bioorganic and Medicinal Chemistry Letters. 2010 ; Vol. 20, No. 12. pp. 3475-3478.
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