Functional examination of novel kisspeptin phosphinic peptides

Zhang, Xiaoyang, Matziari, Magdalini, Xie, Yixin, Fernig, David ORCID: 0000-0003-4875-4293, Rong, Rong, Meng, Jia ORCID: 0000-0003-3455-205X and Lu, Zhi-Liang ORCID: 0000-0002-3442-1415 (2018) Functional examination of novel kisspeptin phosphinic peptides. PLOS ONE, 13 (4). e0195089-.

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Official URL: https://journals.plos.org/plosone/article?id=10.13...

Abstract

Kisspeptins acting on their cognate G protein-coupled receptor, kisspeptin receptor, play important roles in the suppression of cancer cell metastasis and regulation of the reproductive system, and therefore are important for therapeutic intervention. All native functional human kisspeptins (kisspeptin-54, kisspsptin-14 and kisspeptin-13) share the 10 amino acids of kisspeptin-10 at their C-terminus (45–54). However, they are inactivated rapidly by matrix metalloproteinases (MMPs) through the cleavage of the peptide bond between glycine51 and leucine52, which limits their clinical applications. Development of MMP-resistant analogues of kisspeptins may provide better therapeutic outputs. In the present study, two kisspeptin phosphinic peptides were designed and synthesized, and their ability to induce phosphorylation of ERK1/2 through kisspeptin receptor and their inhibition on MMP-2 and MMP-9 whose activity correlates with cancer metastasis were assessed. The results showed that one analogue, phosphinic kisspeptin R isomer (PKPR), exhibited kisspeptin receptor-agonistic activity and also inhibitory activity on MMP-2, indicating that PKPR may serve as a lead for the further development of kisspeptin analogues for therapeutic purpose.

Item Type:	Article
Uncontrolled Keywords:	Phosphorylation, Metastasis, Receptor binding assays, Zinc, Isomers, Amines, Phosphinic acids, Proteases
Depositing User:	Symplectic Admin
Date Deposited:	09 Apr 2018 06:09
Last Modified:	19 Jan 2023 06:36
DOI:	10.1371/journal.pone.0195089
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3019942