PMID: 9523590Apr 2, 1998Paper

Structure-activity relationships of conformationally constrained peptide analogues of loop 2 of brain-derived neurotrophic factor

Journal of Neurochemistry
Paul D O'Leary, R A Hughes

Abstract

Brain-derived neurotrophic factor (BDNF) promotes the survival of various neuronal populations and thus shows potential in the treatment of neurodegenerative disease. However, BDNF is not pharmacokinetically optimal for use as a therapeutic agent. As a step toward the development of low-molecular-weight BDNF-like drugs, we have designed a series of small, conformationally constrained peptides of various sizes using the three-dimensional structure of BDNF derived by homology modeling as a template. When tested in cultures of embryonic chick sensory neurons the peptides produced concentration-dependent inhibition of BDNF-mediated neuronal survival and caused both a rightward shift and depression of the maximum of the BDNF concentration-response curve. The compounds had no effect on the survival response to nerve growth factor and were without intrinsic trophic or toxic effects when added to cultures alone. With the aid of pharmacodynamic simulations we demonstrated that the inhibitory activity of the active peptides is consistent with them acting as competitive antagonists of BDNF for its high-affinity receptor, trkB. An alanine scan of the largest peptide identified several residues important in mediating the inhibitory action o...Continue Reading

Citations

Sep 25, 2012·Bioorganicheskaia khimiia·T A GudashevaS B Seredenin
Nov 6, 2018·Journal of Cellular Biochemistry·Fatemeh NafianBabak Kamali Doust Azad
Apr 2, 2019·Current Pharmaceutical Design·Tatiana A GudashevaSergey B Seredenin
Dec 15, 2005·Physiological Genomics·Dongqing CaiJay M Edelberg
Oct 19, 2013·Bulletin of Experimental Biology and Medicine·I O LogvinovS B Seredenin
Jan 29, 2013·Journal of Neurochemistry·Junhua XiaoSimon S Murray
May 9, 2006·Journal of Peptide Science : an Official Publication of the European Peptide Society·Jordan M Fletcher, Richard A Hughes
Feb 26, 2019·Frontiers in Neuroscience·Sumonto MitraMaria Eriksdotter
Mar 13, 2014·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Joseph P Steiner, Avindra Nath
Sep 24, 2008·The Journal of Biological Chemistry·Jordan M FletcherRichard A Hughes
Dec 2, 2004·The Journal of Biological Chemistry·Gareth WilliamsPatrick Doherty
May 6, 2003·The Journal of Biological Chemistry·Paul D O'Leary, Richard A Hughes
Jul 3, 2021·International Journal of Molecular Sciences·Suzanne GasconNathalie Faucheux
Feb 11, 2020·ACS Omega·Qingqing LinSusan E Northfield

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