Zhongping, University of Colorado Boulder
Chemical Glycoengineering of Human Insulin
Human insulin is widely used for the treatment of diabetes. However, there is often hesitation to initiate insulin therapy because of fear of frequent injections. To address this issue, attempts have been made to develop a less invasive oral route for its administration, and through the use of pH sensitive polymers, insulin can now be efficiently delivered to the small intestine. Currently, one of the major challenges remaining for insulin oral delivery is to improve its absorption in the small intestine. By designing, synthesizing and characterizing a collection of insulin glycoforms with systematically varied O-glycosylation sites and glycan structures, we have demonstrated that O-mannosylation of insulin B-chain Thr27 can improve its properties related to absorption, including reducing its inherent susceptibility to protease degradation and self-association, while at the same time maintaining its biological activity. Overall, our study provides a promising way to develop improved insulin therapy.