PT  - JOURNAL ARTICLE
AU  - Byung-Joon Kim
AU  - Jie Zhou
AU  - Bronwen Martin
AU  - Olga D. Carlson
AU  - Stuart Maudsley
AU  - Nigel H. Greig
AU  - Mark P. Mattson
AU  - Ellen E. Ladenheim
AU  - Jay Wustner
AU  - Andrew Turner
AU  - Homayoun Sadeghi
AU  - Josephine M. Egan
TI  - Transferrin Fusion Technology: A Novel Approach to Prolonging Biological Half-Life of Insulinotropic Peptides
AID  - 10.1124/jpet.110.166470
DP  - 2010 Sep 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 682--692
VI  - 334
IP  - 3
4099  - http://jpet.aspetjournals.org/content/334/3/682.short
4100  - http://jpet.aspetjournals.org/content/334/3/682.full
SO  - J Pharmacol Exp Ther2010 Sep 01; 334
AB  - 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.