Precise structural elucidation of dehydroaltenusin, a specific inhibitor of mammalian DNA polymerase alpha

Bioorg Med Chem. 2004 Oct 15;12(20):5355-9. doi: 10.1016/j.bmc.2004.07.047.

Abstract

The X-ray crystal structure of dehydroaltenusin, a specific inhibitor of mammalian DNA polymerase alpha, has previously been reported. We show that dehydroaltenusin exists in an equilibrium mixture of two tautomers possessing gamma-lactone or delta-lactone in polar solvents by NMR experiments. Acetylation of dehydroaltenusin afforded two types of diacetates and two types of monoacetate, possessing gamma-lactone or delta-lactone, respectively. The inhibitory activities of these acetate derivatives against DNA polymerase alpha were all much weaker than that of dehydroaltenusin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Benzopyrans / chemistry*
  • Benzopyrans / pharmacology*
  • Crystallography, X-Ray
  • DNA Polymerase I / antagonists & inhibitors*
  • Solvents / chemistry

Substances

  • Benzopyrans
  • Solvents
  • DNA Polymerase I
  • dehydroaltenusin