Apelin is a recently discovered peptide that binds to the apelin (or APJ) G-protein-coupled receptor. Apelin-13 (NH2-QRPRLSHKGPMPF-COOH), one of several cleavage products of the proprotein form of the apelin gene product, is a vasoactive peptide and is one of the most potent endogenous inotropic agents known so far.
After having conducted extensive replica-exchange molecular dynamics and competition binding experiments, N. J. Maximilian Macaluso and Robert C. Glen at the University of Cambridge report the design and evaluation of head-to-tail cyclized analogues of the apelin-13 peptide in the journal ChemMedChem.
"The receptor-bound conformation of apelin, if known, would greatly facilitate the rational design of novel agonists and antagonists at APJ," says Glen. "Interest in apelin as a drug target has greatly increased with recognition of its role in cardiovascular disease, metabolic syndrome, and as a co-receptor for HIV infection."
This combined in silico and in vivo approach revealed that peptides promoting a â turn at the RPRL motif toward the N terminus of apelin-13 show affinity for the APJ receptor, whereas those without this RPRL turn exhibit almost no binding at APJ. This is a critical step in understanding the APJ receptor binding site, which has not yet been identified. The study lays the foundation for not only further development of truncated cyclic peptide analogues of apelin-13, but also the development of non-peptide mimetics.
Author: Robert C. Glen, University of Cambridge (UK), http://www.ch.cam.ac.uk/staff/rcg.html
Title: Exploring the RPRL Motif of Apelin-13 through Molecular Simulation and Biological Evaluation of Cyclic Peptide Analogues
ChemMedChem 2010, 5, No. 8, Permalink to the article: http://dx.doi.org/10.1002/cmdc.201000061
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences