Synthesis of chiral phosphoantigens and their activity in γδ T cell stimulation

Yongcheng Song, Yonghui Zhang, Hong Wang, Amy Raker, John Sanders, Erin Broderick, Allen Clark, Craig Morita, Eric Oldfield

Research output: Contribution to journalArticlepeer-review


γδ T cells expressing Vγ2Vδ2 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 Vγ2Vδ2 T cells was determined by TNF-α 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.

Original languageEnglish (US)
Pages (from-to)4471-4477
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Issue number17
StatePublished - Sep 6 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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