Unexpected inhibition of S-adenosyl-L-homocysteine hydrolase by a guanosine nucleoside

Bioorg Med Chem Lett. 2003 Jun 16;13(12):1985-8. doi: 10.1016/s0960-894x(03)00331-7.

Abstract

A series of shape-modified flexible nucleosides ('fleximers', 1, 2, and 3) was modeled, synthesized and subsequently assayed against S-adenosyl-L-homocysteine hydrolase (SAHase). No inhibitory activity was observed for the adenosine fleximer, which served as a substrate, but moderate inhibitory activity was exhibited by the guanosine fleximers. This is the first known report of a guanosine nucleoside analogue possessing activity against SAHase.

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / metabolism
  • Adenosine / pharmacology
  • Adenosylhomocysteinase / antagonists & inhibitors*
  • Calorimetry / methods
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Guanosine / analogs & derivatives*
  • Guanosine / chemical synthesis
  • Guanosine / pharmacology*
  • Hydrogen Bonding
  • Hydrolysis
  • Inosine / analogs & derivatives
  • Inosine / chemical synthesis
  • Inosine / pharmacology
  • Kinetics
  • Models, Molecular
  • Thermodynamics

Substances

  • Enzyme Inhibitors
  • Guanosine
  • Inosine
  • Adenosylhomocysteinase
  • Adenosine