| RESEARCH |
Compound breaks DNA and sustains the break (+)-Myristinin A (shown) has a remarkable ability to cleave DNA; it also prevents repair of the DNA damage that it causes by inhibiting polymerase , a DNA repair enzyme. Sidney M. Hecht and coworkers at the University of Virginia confirmed this unusual combination of biochemical activities after they carried out the first stereoselective synthesis of the natural product (J. Am. Chem. Soc. 2005, 127, 4140). The total synthesis confirms the structure of the natural product and establishes its absolute stereochemistry. It also makes available sufficient amounts of material for biochemical studies. In cancer therapy based on DNA damage, the goal is to keep the DNA damage from being repaired, Hecht says. Scientists seek inhibitors of polymerase for use as adjuvants to DNA-damaging agents in the clinic to boost their efficacy. "We have in this compound both the DNA-damaging ability and the inhibition of repair," he says. |
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