Deciphering the significant impact of natural glycosylation on human insulin.

ABSTRACT: In the century-long evolution of insulin pharmaceuticals, each transformative advancement in this drug class has been closely tied to the ability to obtain new insulin isoforms for research. Despite this, the recently discovered naturally occurring isoforms of glycosylated human insulin have remained largely unattainable for proper characterization. Herein, we demonstrate for the first time that total chemical synthesis can be used to generate all isoforms. This achievement required maintaining the correct positions of the interchain disulfide bonds while effectively removing protecting groups on complex glycans. Notably, the availability of seven glycoforms reveals the important effects of natural sialylated glycans in suppressing insulin self-association and enhancing its solubility, sur

SUBMITTER: Li Y 

PROVIDER: S-EPMC12648096 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature