2 research outputs found
Nanomolar Inhibitors of Glycogen Phosphorylase Based on β‑d‑Glucosaminyl Heterocycles: A Combined Synthetic, Enzyme Kinetic, and Protein Crystallography Study
Aryl substituted 1-(β-d-glucosaminyl)-1,2,3-triazoles
as well as <i>C</i>-β-d-glucosaminyl 1,2,4-triazoles
and imidazoles were synthesized and tested as inhibitors against muscle
and liver isoforms of glycogen phosphorylase (GP). While the <i>N</i>-β-d-glucosaminyl 1,2,3-triazoles showed
weak or no inhibition, the <i>C</i>-β-d-glucosaminyl
derivatives had potent activity, and the best inhibitor was the 2-(β-d-glucosaminyl)-4(5)-(2-naphthyl)-imidazole with a <i>K</i><sub>i</sub> value of 143 nM against human liver GPa. An X-ray crystallography
study of the rabbit muscle GPb inhibitor complexes revealed structural
features of the strong binding and offered an explanation for the
differences in inhibitory potency between glucosyl and glucosaminyl
derivatives and also for the differences between imidazole and 1,2,4-triazole
analogues