title: Synthesis of analogues of (E)-1-hydroxy-2-methylbut-2-enyl 4-diphosphate, an isoprenoid precursor and human gamma delta T cell activator.
abstract: (E)-1-Hydroxy-2-methyl-but-2-enyl 4-diphosphate (HMBPP) is an intermediate in the non-mevalonate pathway for the biosynthesis of isoprenoids and also serves as a very strong activator of human gamma delta T cells expressing Vgamma9Vdelta2 receptors. This paper describes the synthesis of analogues of HMBPP, in which the diphosphate group is replaced by potential isosteric moieties, i.e., carbamate, N-acyl-N'-oxy sulfamate, or aminosulfonyl carbamate functionalities. The potential of the synthesized analogues to stimulate Vgamma9/Vdelta2 T cell response or to inhibit GcpE and LytB, the last enzymes in the non-mevalonate pathway, was assessed.
authors.affiliation: Laboratory for Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Van Hoof
authors.forename: Carl Jeffrey
authors.initials: CJ
authors.lastname: Lacey
authors.forename: René C
authors.initials: RC
authors.lastname: Röhrich
authors.forename: Jochen
authors.initials: J
authors.lastname: Wiesner
authors.forename: Hassan
authors.initials: H
authors.lastname: Jomaa
authors.forename: Serge
authors.initials: S
authors.lastname: Van Calenbergh
mesh_terms: D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010710:Phosphates / Q000138:chemical synthesis / Q000494:pharmacology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000819:agonists*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D010710:Phosphates; D016692:Receptors, Antigen, T-Cell, gamma-delta