| Autor: |
Yongcheng, Song, Yonghui, Zhang, Hong, Wang, Amy M, Raker, John M, Sanders, Erin, Broderick, Allen, Clark, Craig T, Morita, Eric, Oldfield |
| Rok vydání: |
2004 |
| Předmět: |
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| Zdroj: |
Bioorganicmedicinal chemistry letters. 14(17) |
| ISSN: |
0960-894X |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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