A novel glucagon-like peptide 1 peptide identified from Ophisaurus harti.

Journal of peptide science : an official publication of the European Peptide Society

PubMedID: 23893560

Zhu J, Huang X, Gao H, Bao Q, Zhao Y, Hu JF, Xia G. A novel glucagon-like peptide 1 peptide identified from Ophisaurus harti. J Pept Sci. 2013;19(9):598-605.
Glucagon-like peptide 1 receptor (GLP1R) is a promising target for the treatment of type 2 diabetes. Because of the short half-life of endogenous GLP1 peptide, other GLP1R agonists are considered to be appealing therapeutic candidates. A high-throughput assay has been established to screen for GLP1R agonists in a 60?000-well natural product compound library fractionated from 670 different herbs/materials widely used in traditional Chinese medicines (TCMs). The screening is based on primary screen of GLP1R(+) reporter gene assay with the counter screen in GLP1R(-) cell line. An active fraction, A089-147, was identified from the screening. Fraction A089-147 was isolated from dried Ophisaurus harti, and the fact that its GLP1R agonist activity was sensitive to trypsin treatment indicates its peptidic nature. The active ingredient of A089-147 was later identified as O. harti GLP1 through transcriptome analysis. Chemically synthesized O. harti GLP1 showed GLP1R agonist activity and sensitivity to dipeptidase IV digestion. This study illustrated a comprehensive screening strategy to identify novel GLP1R agonists from TCMs libraries and at the same time underlined the difficulty of identifying a non-peptidic GLP1R agonist. The novel O. harti GLP1 peptide yielded from this study confirmed broader application of TCMs libraries in active peptide identification. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.