Synthesis and immunological evaluation of the 4-β-glucoside of HMBPP

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Giner, Jose-Luis¹  Wang, Hong²  Morita, Craig T.² 

[1] SUNY ESF, Dept Chem, Syracuse, NY 13210 USA

[2] Univ Iowa, Carver Coll Med, Vet Affairs Hlth Care Syst, Div Immunol,Dept Internal Med,Interdisciplinary G, Iowa City, IA 52242 USA

关键词: Glycosides;    Immunology;    Nonmevalonate pathway;    Phosphoantigens;    T cells;   

DOI  :  10.1016/j.bmcl.2011.12.055

来源: Elsevier

【 摘 要 】

HMBPP ((E)-4-hydroxy-3-methyl-2-butenyl pyrophosphate) is a highly potent innate immunogen that stimulates human gamma delta T cells expressing the V gamma 2V delta 2 T cell antigen receptor. To determine if glycoside conjugates of HMBPP retain activity, the 4-beta-glucoside and its acetylated homolog were synthesized and tested for their ability to stimulate gamma delta T cells. The glycoside HMBPP conjugate stimulated human gamma delta T cells with an EC50 of 78 nM. The tetraacetyl glycoside HMBPP conjugate was also active (EC50 = 360 nM). The two isomeric mono-beta-glucosides of the parent (E)-2-methylbut-2-ene-1,4-diol, however, were not active. Thus, HMBPP glycosylated at the 4-OH position stimulates gamma delta T cells as long as the pyrophosphate moiety is present. (C) 2011 Elsevier Ltd. All rights reserved.

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