title: Application of Biocatalysis to on-DNA Carbohydrate Library Synthesis.
abstract: 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.
authors.affiliation: Manchester Institute of Biotechnology and, School of Chemistry, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: Baptiste
authors.initials: B
authors.lastname: Thomas
authors.affiliation: Encoded Library Technologies, NCE Molecular Discovery, R&D, Platform Technology & Science, GlaxoSmithKline, 830 Winter Street, Waltham, MA, 02451, USA.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Lu
authors.affiliation: Manchester Institute of Biotechnology and, School of Chemistry, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: William R
authors.initials: WR
authors.lastname: Birmingham
authors.affiliation: Manchester Institute of Biotechnology and, School of Chemistry, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
authors.affiliation: Manchester Institute of Biotechnology and, School of Chemistry, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Both
authors.affiliation: Manchester Institute of Biotechnology and, School of Chemistry, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: Juana Elizabeth
authors.initials: JE
authors.lastname: Reyes Martinez
authors.affiliation: Medicinal Chemistry, NCE Molecular Discovery, R&D, Platform Technology and Science, GlaxoSmithKline, GlaxoSmithKline Medicines Research Centre, Stevenage, Hertfordshire, SG1 2NY, UK.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Young
authors.affiliation: Encoded Library Technologies, NCE Molecular Discovery, R&D, Platform Technology & Science, GlaxoSmithKline, 830 Winter Street, Waltham, MA, 02451, USA.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Davie
authors.affiliation: Manchester Institute of Biotechnology and, School of Chemistry, The University of Manchester, 131 Princess Street, Manchester, M1 7DN, UK.
authors.forename: Sabine L
authors.initials: SL
authors.lastname: Flitsch
mesh_terms: D055162:Biocatalysis; D002241:Carbohydrates / Q000737:chemistry*; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D006001:Glycoconjugates / Q000737:chemistry / Q000378:metabolism; D006031:Glycosylation; D009439:Neuraminidase / Q000378:metabolism; D010084:Oxidation-Reduction; D010776:Photobacterium / Q000201:enzymology; D012799:Sialyltransferases / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry*; D014349:Trypanosoma cruzi / Q000201:enzymology
chemical_list: D002241:Carbohydrates; D006001:Glycoconjugates; D054852:Small Molecule Libraries; D004247:DNA; D012799:Sialyltransferases; D009439:Neuraminidase
keywords: DNA-encoded libraries; biocatalysis; biotransformation; carbohydrate; glycoconjugate