Synthesis and immunological evaluation of the 4-β-glucoside of HMBPP.
HMBPP ((E)-4-hydroxy-3-methyl-2-butenyl pyrophosphate) is a highly potent innate immunogen that stimulates human γδ T cells expressing the Vγ2Vδ2 T cell antigen receptor. To determine if glycoside conjugates of HMBPP retain activity, the 4-β-glucoside and its acetylated homolog were synthesized and tested for their ability to stimulate γδ T cells. The glycoside HMBPP conjugate stimulated human γδ T cells with an EC(50) of 78nM. The tetraacetyl glycoside HMBPP conjugate was also active (EC(50)=360nM). The two isomeric mono-β-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 γδ T cells as long as the pyrophosphate moiety is present.
Department of Chemistry, State University of New York-ESF, Syracuse, NY 13210, United States. jlginer@syr.edu
José-Luis
JL
Giner
Hong
H
Wang
Craig T
CT
Morita
D002460:Cell Line; D006801:Humans; D010755:Organophosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000276:immunology* / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
C467061:4-hydroxy-3-methyl-2-butenyl diphosphate; D010755:Organophosphates