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.
Original language | English |
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Pages (from-to) | 952-957 |
Number of pages | 6 |
Journal | ChemBioChem |
Volume | 21 |
Issue number | 7 |
DOIs | |
State | Published - Apr 1 2020 |
Bibliographical note
Publisher Copyright:© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Keywords
- HDAC
- glucosylation
- glycosyltransferase
- histone deacetylase
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Organic Chemistry