Active diuretic peptidomimetic insect kinin analogs that contain 尾-turn mimetic motif 4-aminopyroglutamate and lack native peptide bonds

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• 作者：Ronald J. Nachman^a ; ^{nachman@tamu.edu} ; Krzysztof Kaczmarek^a ; ^b ; Janusz Zabrocki^a ; ^b ; Geoffrey M. Coast^a ; ^c ; ^{g.coast@bbk.ac.uk}
• 关键词：Insect management ; Reduced peptide bond ; Cricket ; Malpighian tubule ; Diuresis
• 刊名：Peptides
• 出版年：2012
• 期刊代码：59_01969781
• 类别：neu
• 出版时间：March, 2012
• 卷：34
• 期：1
• 页码：262-265
• 文件大小：254 K

摘要

The multifunctional 鈥榠nsect kinins鈥?of arthropods share the evolutionarily conserved C-terminal pentapeptide core sequence Phe-X¹-X²-Trp-Gly-NH₂, where X¹ = His, Asn, Ser, or Tyr and X² = Ser, Pro, or Ala. Insect kinins regulate diuresis in many species of insects, including the house cricket, Acheta domesticus. Insect kinins, however, are susceptible to fast enzymatic degradation by endogenous peptidases that severely limit their potential use as tools for pest control or for endocrinological studies. To enhance resistance to peptidases, the core insect kinin sequence was structurally modified in this study to replace native peptide bonds susceptible to proteolytic degradation. These modifications include incorporation of two stereochemical variants of the 尾-turn mimetic motif 4-aminogutamate in place of the X¹-X² residues, insertion of a reduced peptide bond between residues Trp-Gly, and replacement of the Phe residue with a hydrocinnamyl group. The resulting biostable, peptidomimetic analogs contain no native peptide bonds and yet retain significant diuretic activity in an in vitro cricket Malpighian tubule fluid secretion assay, matching the efficacy of a native A. domesticus kinin (Achdo-KI). These novel analogs represent ideal new tools for endocrinologists studying arthropod kinin regulated processes in vivo, and provide leads in the development of novel, environmentally friendly pest insect management agents capable of disruption of the critical processes that kinins regulate.