Areawide Pest Management Research Unit, Southern Plains Agricultural Research Center, U.S. Department of Agriculture, 2881 F/B Road, College Station, Texas, USA.
Adv Exp Med Biol. 2010;692:27-48. doi: 10.1007/978-1-4419-6902-6_3.
Insect kinin neuropeptides share a common C-terminal pentapeptide sequence Phe1-Xaa1(2)-Xaa2(3)-Trp4-Gly5-NH2 (Xaa1(2) = His, Asn, Phe, Ser or Tyr; Xaa2(3) = Pro, Ser or Ala) and have been isolated from a number of insects, including species of Dictyoptera, Orthoptera and Lepidoptera. They have been associated with the regulation of such diverse processes as hindgut contraction, diuresis and the release of digestive enzymes. In this chapter, the chemical, conformational and stereochemical aspects of the activity ofthe insect kinins with expressed receptors and/or biological assays are reviewed. With this information, biostable analogs are designed that protect peptidase-susceptible sites in the insect kinin sequence and demonstrate significant retention of activity on both receptor and biological assays. The identification of the most critical residue of the insect kinins for receptor interaction is used to select a scaffold for a recombinant library that leads to identification ofa nonpeptide mimetic analog. C-terminal aldehyde insect kinin analogs modify the activity of the insect kinins leading to inhibition of weight gain and mortality in corn earworm larvae and selective inhibition ofdiuresis in the housefly. Strategies for the modification of insect neuropeptide structures for the enhancement ofthe topical and oral bioavailability of insect neuropeptides and the promotion of time-release from the cuticle and/or foregut are reviewed. Promising mimetic analog leads for the development of selective agents capable of disrupting insect kinin regulated processes are identified that may provide interesting tools for arthropod endocrinologists and new pest insect management strategies in the future.
昆虫激肽神经肽共享一个共同的 C 末端五肽序列 Phe1-Xaa1(2)-Xaa2(3)-Trp4-Gly5-NH2（Xaa1(2)=His、Asn、Phe、Ser 或 Tyr；Xaa2(3)=Pro、Ser 或 Ala），已从包括直翅目、半翅目和鳞翅目等多种昆虫中分离出来。它们与调节后肠收缩、利尿和消化酶释放等多种过程有关。在本章中，综述了具有表达受体和/或生物测定的昆虫激肽的化学、构象和立体化学方面的活性。有了这些信息，就可以设计出具有生物稳定性的类似物，保护昆虫激肽序列中对肽酶敏感的位点，并在受体和生物测定中保持显著的活性。鉴定昆虫激肽与受体相互作用的最关键残基，用于选择重组文库的支架，从而鉴定出非肽模拟类似物。C 末端醛昆虫激肽类似物修饰昆虫激肽的活性，导致玉米穗虫幼虫体重增加和死亡率降低，以及家蝇利尿选择性抑制。还综述了为提高昆虫神经肽的局部和口服生物利用度以及促进从角质层和/或前肠释放而修饰昆虫神经肽结构的策略。确定了有前途的模拟类似物先导，用于开发能够破坏昆虫激肽调节过程的选择性药剂，这可能为节肢动物内分泌学家提供有趣的工具，并为未来的新害虫管理策略提供新的选择。
