Replacing the pyrophosphate group of HMB-PP by a diphosphonate function abrogates Its potential to activate human gammadelta T cells but does not lead to competitive antagonism.
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.
Reichenberg
Armin
A
Jomaa Pharmaka GmbH, Frankfurter Str. 50, D-35392 Giessen, Germany.
Hintz
Martin
M
Kletschek
Yvonne
Y
Kuhl
Tanja
T
Haug
Christian
C
Engel
Rosel
R
Moll
Jens
J
Ostrovsky
Dmitry N
DN
Jomaa
Hassan
H
Eberl
Matthias
M
D001667:Binding, Competitive / Q000187:drug effects; D011756:Diphosphates / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008970:Molecular Weight; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects*
C443995:4-hydroxy-3-methylbut-2-enyl pyrophosphate; D011756:Diphosphates; D007202:Indicators and Reagents