Membrane-induced secondary structures of neuropeptides: a comparison of the solution conformations adopted by agonists and antagonists of the mammalian tachykinin NK1 receptor

Journal of Medicinal Chemistry
T L WhiteheadR P Hicks

Abstract

We present what we believe to be the first documented example of an inducement of distinctly different secondary structure types onto agonists and antagonists selective for the same G-coupled protein receptor using the same membrane-model matrix wherein the induced structures are consistent with those suggested to be biologically active by extensive analogue studies and conventional binding assays. 1H NMR chemical shift assignments for the mammalian NK1 receptor-selective agonists alpha-neurokinin (NKA) and beta-neurokinin (NKB) as well as the mammalian NK1 receptor-selective antagonists [d-Pro2,d-Phe7,d-Trp9]SP and [d-Arg1, d-Pro2,d-Phe7,d-His9]SP have been determined at 600 MHz in sodium dodecyl sulfate (SDS) micelles. The SDS micelle system simulates the membrane-interface environment the peptide experiences when in the proximity of the membrane-embedded receptor, allowing for conformational studies that are a rough approximation of in vivo conditions. Two-dimensional NMR techniques were used to assign proton resonances, and interproton distances were estimated from the observed nuclear Overhauser effects (NOEs). The experimental distances were used as constraints in a molecular dynamics and simulated annealing protocol usin...Continue Reading

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Citations

Oct 22, 2002·Biopolymers·Jonathan W Neidigh, Niels H Andersen
Jun 5, 2002·Journal of Peptide Science : an Official Publication of the European Peptide Society·Sylwia Rodziewicz-MotowidłoKrzysztof Rolka
Jan 14, 2003·Biophysical Journal·R Christy Rani GraceSudha M Cowsik
Mar 14, 2001·Journal of Biomolecular Structure & Dynamics·R C GraceS M Cowsik
Dec 25, 2003·Journal of Biomolecular Structure & Dynamics·Tracy L WhiteheadRickey P Hicks
Aug 20, 2004·Journal of Biomolecular Structure & Dynamics·Anil K ManthaSudha M Cowsik
Dec 21, 2007·Journal of Biomolecular Structure & Dynamics·Anjali Dike, Sudha M Cowsik
Apr 4, 2007·Journal of Neurochemistry·Sannah ZoffmannJean-Luc Galzi
Nov 4, 2004·Journal of Structural Biology·Indu R ChandrashekarSudha M Cowsik
May 5, 2009·Journal of Structural Biology·Anjali D Ganjiwale, Sudha M Cowsik
Dec 4, 2003·Biophysical Journal·Indu R Chandrashekar, Sudha M Cowsik
Jan 21, 2017·Physical Chemistry Chemical Physics : PCCP·A Y Pereverzev, O V Boyarkin
Aug 25, 2015·Biopolymers·Anjali Ganjiwale, Sudha M Cowsik
Sep 22, 2001·Journal of Biomolecular Structure & Dynamics·A B PatelR S Phadke
Sep 14, 2018·Current Medicinal Chemistry·Charlene Gadais, Steven Ballet
Sep 18, 2002·Biochemistry·Amy L UlfersDale F Mierke
Jun 6, 2007·Journal of Medicinal Chemistry·Rickey P HicksAlan J Magill
Dec 11, 2007·Journal of Medicinal Chemistry·Debbie J BeardJohn K Young

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