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Application of Biocatalysis to on‐DNA Carbohydrate Library Synthesis
Author(s) -
Thomas Baptiste,
Lu Xiaojie,
Birmingham William R.,
Huang Kun,
Both Peter,
Reyes Martinez Juana Elizabeth,
Young Robert J.,
Davie Christopher P.,
Flitsch Sabine L.
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600678
Subject(s) - biocatalysis , chemical space , chemistry , biomolecule , synthetic biology , chemical biology , combinatorial chemistry , dna , nanotechnology , computational biology , drug discovery , biochemical engineering , biochemistry , biology , reaction mechanism , materials science , catalysis , engineering
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.