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
A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich
New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
20.02.2017 | Materials Sciences
20.02.2017 | Health and Medicine
20.02.2017 | Health and Medicine