Description
Synthetic and natural alkyl phosphates, also known as phosphoantigens, stimulate the proliferation of γδ-T lymphocytes.
1 Isopentenyl pyrophosphate, and related derivatives including (E)-hydroxy-dimethyl-allyl pyrophosphate ((E)-HDMAPP), are particularly effective activators of γδ-
T cells.
2,3 (E)-C-HDMAPP is the pyrophosphonate form of (E)-HDMAPP. The pyrophosphonate moiety in (E)-C-HDMAPP is much less susceptible to chemical or enzymatic hydrolysis than its pyrophosphate counterpart. As a result, (E)-C-HDMAPP is much more stable in solution and in vascular circulation.
4 (E)-C-HDMAPP possesses comparable activity to (E)-HDMAPP, which is the most potent of the isoprenoid phosphoantigens. (E)-C-HDMAPP stimulates the synthesis of tumor necrosis factor (TNF-α) by γδ-T lymphocytes with an IC
50 value of 0.91 nM.
4 (E)-C-HDMAPP also significantly increases the number of circulating γδ-T cells
in vivo, in cynomolgus monkeys.
4
References
1. Tanaka, Y., Sano, S., Nieves, E., et al. Nonpeptide ligands for human γδ T cells Proc. Natl. Acad. Sci. USA 91(17),8175-8179(1994).
2. Poupot, M., and Fournié, J.J. Non-peptide antigens activating human Vγ9/Vδ2 T lymphocytes Immunol. Lett. 95(2),129-138(2004).
3. Tanaka, Y., Morita, C.T., Tanaka, Y., et al. Natural and synthetic non-peptide antigens recognized by human γδ T cells Nature 375(6527),155-158(1995).
4. Bo?dec, A., Sicard, H., Dessolin, J., et al. Synthesis and biological activity of phosphonate analogues and geometric isomers of the highly potent phosphoantigen (E)-1-hydroxy-2-methylbut-2-enyl 4-diphosphate J. Med. Chem. 51(6),1747-1754(2008).