(+)-Myristinin A, a naturally occurring DNA polymerase beta inhibitor and potent DNA-damaging agent

J Am Chem Soc. 2005 Mar 30;127(12):4140-1. doi: 10.1021/ja042727j.

Abstract

The first stereoselective total synthesis of the naturally occurring flavan myristinin A has been accomplished, as well as its biochemical evaluation. This synthesis verified the structural assignment and allowed for the determination of the absolute stereochemistry. Myristinin A exhibits biochemical activity both as a potent DNA-damaging agent and DNA polymerase beta inhibitor. Relaxation of supercoiled plasmid DNA was observed at picomolar concentrations, in addition to inhibition of polymerase beta at low micromolar concentrations.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • DNA Damage*
  • DNA Polymerase beta / antagonists & inhibitors*
  • DNA, Superhelical / drug effects
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / chemical synthesis*
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Myristicaceae / chemistry
  • Stereoisomerism

Substances

  • DNA, Superhelical
  • Enzyme Inhibitors
  • Flavonoids
  • myristinin A
  • DNA Polymerase beta