Zwitterionic Polymer Conjugated Glucagon-like Peptide-1 for Prolonged Glycemic Control.

Bioconjugate Chemistry
Caroline TsaoShaoyi Jiang

Abstract

Glucagon-like peptide-1 (GLP-1) is of particular interest for treating type 2 diabetes mellitus (T2DM), as it induces insulin secretion in a glucose-dependent fashion and has the potential to facilitate weight control. However, native GLP-1 is a short incretin peptide that is susceptible to fast proteolytic inactivation and rapid clearance from the circulation. Various GLP-1 analogs and bioconjugation of GLP-1 analogs have been developed to counter these issues, but these modifications are frequently accompanied by the sacrifice of potency and the induction of immunogenicity. Here, we demonstrated that with the conjugation of a zwitterionic polymer, poly(carboxybetaine) (pCB), the pharmacokinetic properties of native GLP-1 were greatly enhanced without serious negative effects on its potency and secondary structure. The pCB conjugated GLP-1 further provided glycemic control for up to 6 days in a mouse study. These results illustrate that the conjugation of pCB could realize the potential of using native GLP-1 for prolonged glycemic control in treating T2DM.

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Citations

Feb 5, 2021·International Journal of Biological Macromolecules·Jiaman TengYantao Chen
Nov 6, 2021·Journal of Molecular Recognition : JMR·Manjeet Harijan, Meenakshi Singh
Jan 6, 2022·Langmuir : the ACS Journal of Surfaces and Colloids·Yuting LiuYantao Chen

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