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[摘要]：To discover chemical probes to further understand the function of individual DNA polymerases,, we established a generally applicable high-throughput screening. By applying this technique we discovered three novel inhibitor classes of human DNA polymerase lambda (DNA Pol lambda), a key enzyme to maintain the genetic integrity of the genome. The rhodanines, classified as an excellent drug scaffold, were found to be the most potent inhibitors for DNA Pol lambda. Importantly, they are up to 10 times less active against the highly similar DNA polymerase beta. We investigated basic structure activity relationships. Furthermore, the rhodanines showed pharmacological activity in two human cancer cell lines. So the here reported small molecules could serve as useful DNA Pol lambda probes and might serve as starting point to develop novel therapeutic agents. |
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