Transferrin fusion technology: A novel approach to prolonging biological half-life of insulinotropic peptides

Byung Joon Kim, Jie Zhou, Bronwen Martin, Olga D. Carlson, Stuart Maudsley, Nigel H. Greig, Mark P. Mattson, Ellen E. Ladenheim, Jay Wustner, Andrew Turner, Homayoun Sadeghi, Josephine M. Egan

Research output: Contribution to journalArticlepeer-review

Abstract

Fusion proteins made up of glucagon-like peptide 1 (GLP-1) and exendin-4 (EX-4) fused to a nonglycosylated form of human transferrin (GLP-1-Tf or EX-4-Tf) were produced and characterized. GLP-1-Tf activated the GLP-1 receptor, was resistant to inactivation by peptidases, and had a half-life of approximately 2 days, compared with 1 to 2 min for native GLP-1. GLP-1-Tf retained the acute, glucose-dependent insulin-secretory properties of native GLP-1 in diabetic animals and had a profound effect on proliferation of pancreatic β-cells. In addition, Tf and the fusion proteins did not cross the blood-brain-barrier but still reduced food intake after peripheral administration. EX-4-Tf proved to be as effective as EX-4 but had longer lived effects on blood glucose and food intake. This novel transferrin fusion technology could improve the pharmacology of various peptides.

Original languageEnglish (US)
Pages (from-to)682-692
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume334
Issue number3
DOIs
StatePublished - Sep 2010

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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