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OleD Loki as a Catalyst for Hydroxamate Glycosylation
Author(s) -
Hughes Ryan R.,
Shaaban Khaled A.,
Ponomareva Larissa V.,
Horn Jamie,
Zhang Chunhui,
Zhan ChangGuo,
Voss S. Randal,
Leggas Markos,
Thorson Jon S.
Publication year - 2020
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.201900601
Subject(s) - glycosylation , chemistry , histone deacetylase , glycosyl , enzyme , biochemistry , cytotoxicity , docking (animal) , glycosyltransferase , oxazoline , combinatorial chemistry , substrate (aquarium) , catalysis , histone , biology , medicine , nursing , in vitro , ecology , gene
Abstract Herein we describe the ability of the permissive glycosyltransferase (GT) OleD Loki to convert a diverse set of >15 histone deacetylase (HDAC) inhibitors (HDACis) into their corresponding hydroxamate glycosyl esters. Representative glycosyl esters were subsequently evaluated in assays for cancer cell line cytotoxicity, chemical and enzymatic stability, and axolotl embryo tail regeneration. Computational substrate docking models were predictive of enzyme‐catalyzed turnover and suggest certain HDACis may form unproductive, potentially inhibitory, complexes with GTs.