Engineering of a VPAC2 Receptor Peptide Agonist To Impart Dipeptidyl Peptidase IV Stability and Enhance in Vivo Glucose Disposal
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- 作者：Kevin B. Clairmont ; Thomas M. Buckholz ; Carla M. Pellegrino ; Joanne M. Buxton ; Nicole Barucci ; Andrea Bell ; Sha Ha ; Fugang Li ; Thomas H. Claus ; Arthur I. Salhanick ; Kevin J. Lumb
- 刊名：Journal of Medicinal Chemistry
- 出版年：2006
- 出版时间：December 14, 2006
- 年：2006
- 卷：49
- 期：25
- 页码：7545 - 7548
- 全文大小：70K
- 年卷期：v.49,no.25(December 14, 2006)
- ISSN：1520-4804
文摘
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 ofVPAC2P-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 exhibitssubstantially improved half-life and glucose disposal in rodents. Ac-VPAC2P-PEG has therapeutic potentialfor diabetes management.