(+)-Myristinin A, a naturally occurring DNA polymerase beta inhibitor and potent DNA-damaging agent |
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| Authors: | Maloney David J Deng Jing-Zhen Starck Shelley R Gao Zhijie Hecht Sidney M |
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| Affiliation: | Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901, USA. |
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| 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. |
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