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New CD1d agonists: synthesis and biological activity of 6″-triazole-substituted α-galactosyl ceramides.

Abstract：

:Huisgen [3+2] dipolar cycloaddition of 6″-azido-6″-deoxy-α-galactosyl ceramide 11 with a range of alkynes (or a benzyne precursor) yielded a series of triazole-containing α-galactosyl ceramide (α-GalCer) analogues in high yield. These α-GalCer analogues and the precursor azide 11 were tested for their ability to activate iNKT cells and stimulate IL-2 cytokine secretion in vitro, and IFN-γ and IL-4 cytokine secretion in vivo. Some of these analogues, specifically 11, 12b, 12f and 13, were more potent IL-2 stimulators than the prototypical CD1d agonist, α-GalCer 1. In terms of any cytokine bias, most of the triazole-containing analogues exhibited a small Th2 cytokine-biasing response relative to that shown by α-GalCer 1. In contrast, the cycloaddition precursor, namely azide 11, provided a small Th1 cytokine-biasing response.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Jervis PJ,Graham LM,Foster EL,Cox LR,Porcelli SA,Besra GS

doi

10.1016/j.bmcl.2012.05.009

subject

Has Abstract

pub_date

2012-07-01 00:00:00

pages

4348-52

issue

13

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(12)00599-9

journal_volume

22

pub_type

杂志文章

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