Application of Biocatalysis to on-DNA Carbohydrate Library Synthesis.
DNA-encoded libraries are increasingly used for the discovery of bioactive lead compounds in high-throughput screening programs against specific biological targets. Although a number of libraries are now available, they cover limited chemical space due to bias in ease of synthesis and the lack of chemical reactions that are compatible with DNA tagging. For example, compound libraries rarely contain complex biomolecules such as carbohydrates with high levels of functionality, stereochemistry, and hydrophilicity. By using biocatalysis in combination with chemical methods, we aimed to significantly expand chemical space and generate generic libraries with potentially better biocompatibility. For DNA-encoded libraries, biocatalysis is particularly advantageous, as it is highly selective and can be performed in aqueous environments, which is an essential feature for this split-and-mix library technology. In this work, we demonstrated the application of biocatalysis for the on-DNA synthesis of carbohydrate-based libraries by using enzymatic oxidation and glycosylation in combination with traditional organic chemistry.
['Thomas|Baptiste|B|', 'Lu|Xiaojie|X|', 'Birmingham|William R|WR|', 'Huang|Kun|K|', 'Both|Peter|P|', 'Reyes Martinez|Juana Elizabeth|JE|', 'Young|Robert J|RJ|', 'Davie|Christopher P|CP|', 'Flitsch|Sabine L|SL|']
D055162:Biocatalysis D002241:Carbohydrates D004247:DNA D006001:Glycoconjugates D006031:Glycosylation D009439:Neuraminidase D010084:Oxidation-Reduction D010776:Photobacterium D012799:Sialyltransferases D054852:Small Molecule Libraries D014349:Trypanosoma cruzi
biocatalysis carbohydrate DNA-encoded libraries biotransformation glycoconjugate