In Vitro and In Silico Studies of Human Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) Inhibition by Stereoisomeric Forms of Lipophilic Nucleosides: The Role of Carbohydrate Stereochemistry in Ligand-Enzyme Interactions.
Nadezhda S DyrkheevaIrina A ChernyshovaGeorgy A IvanovYuri B PorozovAnastasia A ZenchenkoVladimir E OslovskyAlexandra L ZakharenkoDarina I NasyrovaGalina N LikhatskayaSergey N MikhailovOlga I LavrikMikhail S DrenichevPublished in: Molecules (Basel, Switzerland) (2022)
Inhibition of human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1) by different chiral lipophilic nucleoside derivatives was studied. New Tdp1 inhibitors were found in the series of the studied compounds with IC 50 = 2.7-6.7 μM. It was shown that D-lipophilic nucleoside derivatives manifested higher inhibition activity than their L-analogs, and configuration of the carbohydrate moiety can influence the mechanism of Tdp1 inhibition.