Journal article
Synthesis of chiral phosphoantigens and their activity in gamma delta T cell stimulation
Bioorganic & medicinal chemistry letters, Vol.14(17), pp.4471-4477
09/06/2004
DOI: 10.1016/j.bmcl.2004.06.052
PMID: 15357974
Abstract
Gammadelta T cells expressing Vgamma2Vdelta2 T cell receptors are activated by a broad range of phosphorus-containing small molecules, termed phosphoantigens, and are of interest in the context of the chemotherapy of B cell malignancies. Here, we report the synthesis of four pairs of chiral phosphoantigens: the bromohydrins of isopentenyl diphosphate (Phosphostim), the epoxides of isopentenyl diphosphate (EIPP); and the corresponding bromohydrin and epoxide analogs of but-3-enyl diphosphate. The ability of each compound to stimulate human Vgamma2Vdelta2 T cells was determined by TNF-alpha release and cell proliferation. In these assays, the (R)-bromohydrin diphosphates were, on average, about twice as active as the (S)-bromohydrin diphosphates. In contrast, the (S)-form of EIPP was about twice as active as (R)-EIPP. The activities of the epoxy but-3-enyl diphosphates were both very low. These results suggest that chiral phosphoantigens, as opposed to racemic mixtures, may have utility in immunotherapy.
Details
- Title: Subtitle
- Synthesis of chiral phosphoantigens and their activity in gamma delta T cell stimulation
- Creators
- Yongcheng Song - Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, 61801, USAHong WangYonghui ZhangAmy M RakerJohn M SandersErin BroderickAllen ClarkCraig T MoritaEric Oldfield
- Resource Type
- Journal article
- Publication Details
- Bioorganic & medicinal chemistry letters, Vol.14(17), pp.4471-4477
- DOI
- 10.1016/j.bmcl.2004.06.052
- PMID
- 15357974
- ISSN
- 0960-894X
- eISSN
- 1464-3405
- Language
- English
- Date published
- 09/06/2004
- Academic Unit
- Immunology; Internal Medicine
- Record Identifier
- 9984094618402771
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