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

Bioorg Med Chem Lett. 2003 Apr 7;13(7):1257-60. doi: 10.1016/s0960-894x(03)00138-0.

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.

MeSH terms

  • Binding, Competitive / drug effects
  • Diphosphates / chemistry
  • Diphosphates / pharmacology*
  • Humans
  • In Vitro Techniques
  • Indicators and Reagents
  • Magnetic Resonance Spectroscopy
  • Molecular Weight
  • Structure-Activity Relationship
  • T-Lymphocytes / drug effects*

Substances

  • 4-hydroxy-3-methylbut-2-enyl pyrophosphate
  • Diphosphates
  • Indicators and Reagents