Rational Design of Dual-Domain Binding Inhibitors for <i>N</i>-Acetylgalactosamine Transferase 2 with Improved Selectivity over the T1 and T3 Isoforms.

ABSTRACT: The GalNAc-transferase (GalNAc-T) family, consisting of 20 isoenzymes, regulates the O-glycosylation process of mucin glycopeptides by transferring GalNAc units to serine/threonine residues. Dysregulation of specific GalNAc-Ts is associated with various diseases, making these enzymes attractive targets for drug development. The development of inhibitors is key to understanding the implications of GalNAc-Ts in human diseases. However, developing selective inhibitors for individual GalNAc-Ts represents a major challenge due to shared structural similarities among the isoenzymes and some degree of redundancy among the natural substrates. Herein, we report the development of a GalNAc-T2 inhibitor with higher potency compared to those of the T1 and T3 isoforms. The most promising candida

SUBMITTER: Companon I 

PROVIDER: S-EPMC11423303 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature