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
The balancing act: An enzyme that links endocytosis to membrane recycling
07.12.2016 | National Centre for Biological Sciences
Transforming plant cells from generalists to specialists
07.12.2016 | Duke University
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
07.12.2016 | Health and Medicine
07.12.2016 | Life Sciences
07.12.2016 | Health and Medicine