Development of novel G-protein-coupled receptor 54 agonists with resistance to degradation by matrix metalloproteinase.

Authors

• Kenji Tomita
• Shinya Oishi
• Hiroaki Ohno
• Stephen C Peiper
• Nobutaka Fujii

Publication/Presentation Date

12-11-2008

Abstract

Kisspeptin-GPR54 signaling is involved in the suppression of cancer metastasis and regulation of hormonal secretion. Recently, matrix metalloproteinase mediated deactivation of kisspeptins through hydrolysis of the Gly-Leu peptide bond has been reported. In the present report, GPR54 agonistic peptides having several nonhydrolyzable Gly-Leu dipeptide isosteres were designed and synthesized. (E)-Alkene- and hydroxyethylene-type isostere-containing analogues maintained the original activity with higher stability in murine serum and resistance to MMP-9-mediated cleavage.

Volume

51

Issue

23

First Page

7645

Last Page

7649

ISSN

1520-4804

Published In/Presented At

Tomita, K., Oishi, S., Ohno, H., Peiper, S. C., & Fujii, N. (2008). Development of novel G-protein-coupled receptor 54 agonists with resistance to degradation by matrix metalloproteinase. Journal of medicinal chemistry, 51(23), 7645–7649. https://doi.org/10.1021/jm800930w

Disciplines

Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods

PubMedID

19007202

Department(s)

Administration and Leadership

Document Type

Article