1. Engineering of a VPAC2 receptor peptide agonist to impart dipeptidyl peptidase IV stability and enhance in vivo glucose disposal.
- Author
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Clairmont KB, Buckholz TM, Pellegrino CM, Buxton JM, Barucci N, Bell A, Ha S, Li F, Claus TH, Salhanick AI, and Lumb KJ
- Subjects
- Acetylation, Animals, CHO Cells, Cricetinae, Cricetulus, Half-Life, Humans, Hydrolysis, Hypoglycemic Agents chemistry, Hypoglycemic Agents pharmacology, Insulin Secretion, Male, Peptides chemistry, Peptides pharmacology, Radioligand Assay, Rats, Rats, Wistar, Receptors, Vasoactive Intestinal Peptide, Type II metabolism, Dipeptidyl Peptidase 4 metabolism, Glucose metabolism, Hypoglycemic Agents chemical synthesis, Insulin metabolism, Peptides chemical synthesis, Receptors, Vasoactive Intestinal Peptide, Type II agonists
- Abstract
VPAC2P-PEG is a VPAC2 receptor agonist peptide that acts as a glucose-dependent insulin secretagogue. Proteolysis by DPPIV may contribute to the in vivo clearance of VPAC2P-PEG. Here, the N-terminus of VPAC2P-PEG is modified by N-terminal acetylation to impart DPPIV resistance. The acetylated peptide, Ac-VPAC2P-PEG, is a selective and potent VPAC2 agonist, resistant to DPPIV proteolysis, and exhibits substantially improved half-life and glucose disposal in rodents. Ac-VPAC2P-PEG has therapeutic potential for diabetes management.
- Published
- 2006
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