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.
|Number of pages||6|
|State||Published - Apr 1 2020|
Bibliographical noteFunding Information:
This work was supported in part by US National Institutes of Health (NIH) grants R37 AI52218 (J.S.T.) and R24 OD21479 (S.R.V. and J.S.T.), the National Center for Advancing Translational Sciences (UL1 TR000117 and UL1 TR001998), and the University of Kentucky College of Pharmacy. We thank the College of Pharmacy NMR Center (University of Kentucky) for NMR support.
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
- histone deacetylase
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Organic Chemistry