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

José-Luis Giner; Hong Wang; Craig T Morita

doi:10.1016/j.bmcl.2011.12.055

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

Journal article

Peer reviewed

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

José-Luis Giner, Hong Wang and Craig T Morita

Bioorganic & medicinal chemistry letters, Vol.22(2), pp.811-813

01/15/2012

DOI: 10.1016/j.bmcl.2011.12.055

PMCID: PMC3465662

PMID: 22222033

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https://www.ncbi.nlm.nih.gov/pmc/articles/3465662View

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Abstract

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.

Organophosphates - pharmacology

Cell Line

T-Lymphocytes - drug effects

Humans

Organophosphates - chemical synthesis

Organophosphates - immunology

Organophosphates - chemistry

T-Lymphocytes - immunology

Details

Title: Subtitle: Synthesis and immunological evaluation of the 4-β-glucoside of HMBPP
Creators: José-Luis Giner - Department of Chemistry, State University of New York-ESF, Syracuse, NY 13210, United States. jlginer@syr.edu
Hong Wang
Craig T Morita
Resource Type: Journal article
Publication Details: Bioorganic & medicinal chemistry letters, Vol.22(2), pp.811-813
DOI: 10.1016/j.bmcl.2011.12.055
PMID: 22222033
PMCID: PMC3465662
NLM abbreviation: Bioorg Med Chem Lett
ISSN: 0960-894X
eISSN: 1464-3405
Grant note: R01 AR045504-06 / NIAMS NIH HHS R01 AR045504-10 / NIAMS NIH HHS AR045504 / NIAMS NIH HHS R01 CA113874-03 / NCI NIH HHS R01 CA113874-01 / NCI NIH HHS R01 AR045504-07 / NIAMS NIH HHS R01 CA113874 / NCI NIH HHS R01 AR045504 / NIAMS NIH HHS R01 AR045504-09 / NIAMS NIH HHS R01 AR045504-11 / NIAMS NIH HHS CA113874 / NCI NIH HHS R03 AR045095-04 / NIAMS NIH HHS R01 CA113874-04 / NCI NIH HHS I01 BX000972 / BLRD VA R01 CA113874-02 / NCI NIH HHS R01 AR045504-08 / NIAMS NIH HHS
Language: English
Date published: 01/15/2012
Academic Unit: Immunology; Internal Medicine
Record Identifier: 9984094361502771

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