Jump to main content
Jump to site search
Access to RSC content Close the message box

Continue to access RSC content when you are not at your institution. Follow our step-by-step guide.


Issue 2, 2017
Previous Article Next Article

Structure–activity relationship of novel macrocyclic biased apelin receptor agonists

Author affiliations

Abstract

Apelin is the endogenous ligand for the G protein-coupled receptor APJ and exerts a key role in regulating cardiovascular functions. We report herein a novel series of macrocyclic analogues of apelin-13 in which the N- and C-terminal residues as well as the macrocycle composition were chemically modified to modulate structure–activity relationships on the APJ receptor. To this end, the binding affinity and the ability to engage G protein-dependent and G protein-independent signalling pathways of the resulting analogues were assessed. In this series, the position and the nature of the C-terminal aromatic residue is a determinant for APJ interaction and β-arrestin recruitment, as previously demonstrated for linear apelin-13 derivatives. We finally discovered compounds 1, 4, 11 and 15, four potent G protein-biased apelin receptor agonists exhibiting affinity in the nanomolar range for APJ. These macrocyclic compounds represent very useful pharmacological tools to explore the therapeutic potential of the apelinergic system.

Graphical abstract: Structure–activity relationship of novel macrocyclic biased apelin receptor agonists

Back to tab navigation

Supplementary files

Article information


Submitted
14 Oct 2016
Accepted
29 Nov 2016
First published
29 Nov 2016

Org. Biomol. Chem., 2017,15, 449-458
Article type
Paper

Structure–activity relationship of novel macrocyclic biased apelin receptor agonists

A. Murza, X. Sainsily, J. Côté, L. Bruneau-Cossette, É. Besserer-Offroy, J. Longpré, R. Leduc, R. Dumaine, O. Lesur, M. Auger-Messier, P. Sarret and É. Marsault, Org. Biomol. Chem., 2017, 15, 449
DOI: 10.1039/C6OB02247B

Social activity

Search articles by author

Spotlight

Advertisements