Stability of Synthetic Exendin-4 in Human Plasma in Vitro

Abstract

Abstract: Synthetic exendin-4 exhibits dose-dependent glucose-regulatory activity similar to that of native glucagon-like peptide-1(GLP-1). Moreover, exendin-4 is resistant to degradation by dipeptidyl peptidase-Ⅳ(DPP-Ⅳ) while GLP-1 is degraded by DPP-Ⅳ with a half-life of less than 2 min in mammals. In this study the stability of exendin-4 in human plasma was evaluated in vitro. Exendin-4 was incubated in plasma at 37 ℃, extracted and subsequently analyzed by using high performance liquid chromatography(HPLC). Exendin-4 was slowly broken down in plasma. Its half-life time is 9.57 h. The degradation products were identified by mass-spectrum(MS). According to natural sequence of exendin-4, we deduced that the cleavage were between the Thr⁵ and Phe⁶ bond, Phe⁶ and Thr⁷ bond, and Thr⁷ and Ser⁸ bond of the N-terminus region of the peptide, and the results of ESI-TOF-MS prove that our primary conclusion was correct.

Key words: Exendin-4, Glucagon-like peptide, Dipeptidyl peptidase-Ⅳ, Stability

CLC Number:

O629

TrendMD:

CHEN Jie, LI Wei, YU Ling, WANG Li-Ping*. Stability of Synthetic Exendin-4 in Human Plasma in Vitro[J]. Chem. J. Chinese Universities, doi: .

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Stability of Synthetic Exendin-4 in Human Plasma in Vitro

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