PMID: 9190285Feb 1, 1997Paper

Consensus chemistry and beta-turn conformation of the active core of the insect kinin neuropeptide family

Chemistry & Biology
V A RobertsJ A Tainer

Abstract

Neuropeptides are examples of small, flexible molecules that bind to receptors and induce signal transduction, thereby eliciting biological activity. The multifunctional insect kinin neuropeptides retain full activity when reduced to only their carboxy-terminal pentapeptide (Phe1-X2-X3-Trp4-Gly5-NH2), thereby allowing extensive structure-function studies and conformational analysis. A combined experimental and theoretical analysis of the insect kinin carboxy-terminal pentapeptide was used to probe the role of each residue, define the bioactive conformation, and design a constrained bioactive analog. Coupling receptor-binding data with two biological activity assays allowed receptor binding and signal transduction to be differentiated. A preferred beta-turn conformation, found for residues 1-4 by molecular dynamics simulations, was tested by designing a conformationally restricted cyclic hexapeptide. This cyclic analog showed a preference for the beta-turn conformation, as shown by a conformational search and nuclear magnetic resonance spectroscopy, and it showed stronger receptor binding but decreased activity relative to highly active linear analogs. Each residue of the insect kinin carboxy-terminal pentapeptide has a distinct...Continue Reading

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Citations

Oct 25, 2000·Insect Biochemistry and Molecular Biology·P V PietrantonioT K Hayesa
Feb 17, 2000·Annals of the New York Academy of Sciences·P TorfsL Schoofs
Feb 17, 2000·Annals of the New York Academy of Sciences·R J NachmanJ Varden Broeck
Apr 29, 2015·Journal of Agricultural and Food Chemistry·Chuanliang ZhangXinling Yang
Feb 3, 2009·Bioorganic & Medicinal Chemistry·Jürgen Scherkenbeck, Tino Zdobinsky
Jun 5, 2008·Journal of Peptide Science : an Official Publication of the European Peptide Society·Yun HuangShouliang Dong
May 22, 2009·Annals of the New York Academy of Sciences·Ronald J NachmanGeoffrey M Coast
Oct 1, 2009·Chembiochem : a European Journal of Chemical Biology·Tino ZdobinskyHeru Chen
Sep 30, 2009·Journal of Peptide Science : an Official Publication of the European Peptide Society·Jürgen ScherkenbeckHeru Chen
May 8, 1999·The Journal of Peptide Research : Official Journal of the American Peptide Society·G MoynaA I Scott
Aug 2, 2011·Journal of Peptide Science : an Official Publication of the European Peptide Society·Bo ZhangShouliang Dong
Feb 11, 2020·Journal of Proteome Research·Laura A FleitesMichelle L Heck
Nov 6, 2008·General and Comparative Endocrinology·Suparna Taneja-BageshwarRonald J Nachman

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