Replacing the pyrophosphate group of HMB-PP by diphosphonate function abrogates Its potential to activate human gammadelta T cells but does not lead to competitive antagonism

Reichenberg, A., Hintz, M., Kletschek, Y., Kuhl, T., Haug, C., Engel, R., Moll, J., Ostrovsky, D. N., Jomaa, H. and Eberl, Matthias ORCID: https://orcid.org/0000-0002-9390-5348 2003. Replacing the pyrophosphate group of HMB-PP by diphosphonate function abrogates Its potential to activate human gammadelta T cells but does not lead to competitive antagonism. Biorganic and Medicinal Chemistry Letters 13 (7) , pp. 1257-1260. 10.1016/s0960-894x(03)00138-0

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Abstract

The immunological characterization of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), and its methylenediphosphonate analogue, HMB-PCP, is described. With an EC(50) of 0.1-0.2 nM, HMB-PP is significantly more potent in stimulating human Vgamma9/Vdelta2 T cells than any other compound described so far. However, replacing the pyrophosphate by a P-CH(2)-P function abrogates the bioactivity drastically, with HMB-PCP having a EC(50) of only 5.3 microM.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Subjects:	R Medicine > R Medicine (General) R Medicine > RZ Other systems of medicine
Publisher:	Elsevier
ISSN:	0960-894X
Last Modified:	27 Oct 2022 09:00
URI:	https://orca.cardiff.ac.uk/id/eprint/64097

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