title: 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.
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.
authors.affiliation: Jomaa Pharmaka GmbH, Frankfurter Str. 50, D-35392 Giessen, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Reichenberg
authors.forename: Martin
authors.initials: M
authors.lastname: Hintz
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Kletschek
authors.forename: Tanja
authors.initials: T
authors.lastname: Kuhl
authors.forename: Christian
authors.initials: C
authors.lastname: Haug
authors.forename: Rosel
authors.initials: R
authors.lastname: Engel
authors.forename: Jens
authors.initials: J
authors.lastname: Moll
authors.forename: Dmitry N
authors.initials: DN
authors.lastname: Ostrovsky
authors.forename: Hassan
authors.initials: H
authors.lastname: Jomaa
authors.forename: Matthias
authors.initials: M
authors.lastname: Eberl
mesh_terms: 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*
chemical_list: C443995:4-hydroxy-3-methylbut-2-enyl pyrophosphate; D011756:Diphosphates; D007202:Indicators and Reagents