title: (+)-Myristinin A, a naturally occurring DNA polymerase beta inhibitor and potent DNA-damaging agent.
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.
authors.affiliation: Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Maloney
authors.forename: Jing-Zhen
authors.initials: JZ
authors.lastname: Deng
authors.forename: Shelley R
authors.initials: SR
authors.lastname: Starck
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Gao
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Hecht
mesh_terms: D004249:DNA Damage; D019951:DNA Polymerase beta / Q000037:antagonists & inhibitors*; D004278:DNA, Superhelical / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D026324:Myristicaceae / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D005419:Flavonoids; C500691:myristinin A; D019951:DNA Polymerase beta