|Nachman, Ronald - Ron|
Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 4/9/2008
Publication Date: 6/15/2010
Citation: Nachman, R.J., Pietrantonio, P.V. 2010. Interaction of mimetic analogs of insect kinin neuropeptides with arthropod receptors. In: Geary, T.G., Maule, A. G., editors. Neuropeptide Systems as Targets for Parasite and Pest Control. Austin, TX. Landes Bioscience. p. 86-98. Interpretive Summary: Because of problems with the development of resistance to conventional pesticides, there is a critical need for new concepts and alternative approaches in controlling insect pests. The basic premise of this research is that neuropeptides (short chains of amino acids) serve as potent messengers in insects to regulate vital functions. Nevertheless, neuropeptides in and of themselves hold little promise as pest control agents because of susceptibility to being degraded in the target pest. New, selective control measures may be developed by designing metabolically stable mimics of these neuropeptides that interact with the active site within the agricultural or medical pest in such a way as to either inhibit or over-stimulate critical neuropeptide-regulated life functions. This book chapter summarizes recent advances in the development of synthetic mimics of neuropeptides of the insect kinin class with enhanced biostability via novel strategies. These neuropeptide mimics have been shown to interact potently with active sites in both the yellow fever mosquito and the cattle fever tick in either a nonselective, or selective, fashion. Selectivity is an important component of successful and safe pest control methodologies. The work brings us one step closer to the development of practical neuropeptide-like substances that will be effective in controlling pest arthropods in an environmentally friendly fashion.
Technical Abstract: 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, Lepidoptera, and Orthoptera. 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 of the 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 for receptor interaction is used to select a scaffold for a recombinant library that leads to identification of a 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 of diuresis in the housefly. Strategies for the modification of insect neuropeptide structures for the enhancement of the 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 in 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.