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- W2000257306 abstract "Human nuclear uracil DNA glycosylase (UNG2) and deoxyuridine triphosphate nucleotidohydrolase (dUTPase) are the primary enzymes that prevent the incorporation and accumulation of deoxyuridine in genomic DNA. These enzymes are desirable targets for small molecule inhibitors given their roles in a wide range of biological processes ranging from chromosomal rearrangements that lead to cancer, viral DNA replication, and the formation of toxic DNA strand breaks during anticancer drug therapy. To accelerate the discovery of such inhibitors, we have developed a high-throughput approach for directed library synthesis and screening. In this efficient technology, a uracil-aldehyde ligand is covalently tethered to one position of a trivalent alkyloxyamine linker via an oxime linkage, and then the vacant linker positions are derivatized with a library of aldehydes. The resulting triskelion oximes were directly screened for inhibitory activity and the most potent of these showed micromolar binding affinities to UNG2 and dUTPase." @default.
- W2000257306 created "2016-06-24" @default.
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- W2000257306 date "2006-08-01" @default.
- W2000257306 modified "2023-09-25" @default.
- W2000257306 title "Synthesis and high-throughput evaluation of triskelion uracil libraries for inhibition of human dUTPase and UNG2" @default.
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- W2000257306 doi "https://doi.org/10.1016/j.bmc.2006.04.022" @default.
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