Heteroaromatic Moieties in the Sphingosine Backbone of α-Galactosylceramides for Noncovalent Interactions with CD1d

Yongju Kim; Jonghoon Kim; Keunhee Oh; Dong-Sup Lee; Seung Bum Park

doi:10.1021/ml200278u

Heteroaromatic Moieties in the Sphingosine Backbone of α-Galactosylceramides for Noncovalent Interactions with CD1d

ACS Med Chem Lett. 2012 Jan 10;3(2):151-4. doi: 10.1021/ml200278u. eCollection 2012 Feb 9.

Authors

Yongju Kim¹, Jonghoon Kim¹, Keunhee Oh², Dong-Sup Lee², Seung Bum Park³

Affiliations

¹ Department of Chemistry, Seoul National University , Seoul, Korea.
² Department of Biomedical Sciences, Seoul National University College of Medicine , Seoul, Korea.
³ Department of Chemistry, Seoul National University , Seoul, Korea ; Department of Biophysics and Chemical Biology/Bio-MAX Institute, Seoul National University , Seoul, Korea.

Abstract

A series of α-GalCer analogues containing heterocyclic and aromatic moieties in the sphingosine backbone were synthesized to improve the selectivity in the Th1/Th2 cytokine profile via noncovalent interaction with three aromatic residues at the binding pocket of CD1d. In vitro and in vivo biological evaluations revealed the treatment of α-GalCer analogue (6) induced the selective stimulation of natural killer T cells to facilitate the secretion of Th2 cytokines.

Keywords: CD1d; cytokine secretion; noncovalent interaction; selectivity; α-Galactosylceramide.