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United States Department of Agriculture

Agricultural Research Service

Title: Structure-Activity Relationships for Insect Kinins on Expressed Receptors from a Tick (Acari:ixodidae) and a Mosquito (Diptera:culicidae)

Authors
item Taneja-Bageshwar, Suparna - TEXAS A&M UNIV
item Strey, Allison
item Zubrzak, Pawel - TECHNICAL UNIV, POLAND
item Pietrantonio, Patricia - TEXAS A&M UNIV
item Nachman, Ronald

Submitted to: International Conference on Arthropods Chemical Physiological ...
Publication Type: Proceedings
Publication Acceptance Date: December 22, 2005
Publication Date: April 15, 2006
Citation: Taneja-Bageshwar, S., Strey, A.A., Zubrzak, P., Pietrantonio, P.V., Nachman, R.J. 2006. Structure-activity relationships for insect kinins on expressed receptors from a tick (Acari: Ixodidae) and a mosquito (Diptera: Culicidae). Proceedings of International Conference on Arthropods: Chemical, Physiological and Environmental Perspectives. 3:55-59.

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 invertebrate pests such as insects and ticks. The basic premise of this research is that neuropeptides (short chains of amino acids) serve as potent messengers in invertebrates such as ticks and 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. We must design neuropeptide mimics that resist degradation by enzymes in the digestive tract and blood of pest invertebrates and interact with the active site within the agricultural or medical pest in such a way as to either over-activate or block critical, neuropeptide-regulated life functions. We report on a comparison of the molecular characteristics required for neuropeptides of the insect kinin class to interact with active sites in a mosquito and a tick, medical pests that plague man and livestock. Included in this study is the identification of a potent modified neuropeptide with enhanced resistance to degradation within the target pest. This biostable version of the neuropeptide can serve as a tool to further understand the role of this neuropeptide class in regulating water balance in the mosquito; and to understand their function in ticks, for which nothing is known. This discovery will aid in the design of neuropeptide-like compounds capable of disrupting critical life functions in insects and ticks. This work brings us one step closer to the development of practical neuropeptide-like substances that will be effective in controlling invertebrate pests, including ticks and insects,in an environmentally friendly fashion.

Technical Abstract: The systematic analysis of structure-activity relationships of insect kinins on two heterologous receptor-expressing systems is described. Previously, kinin receptors from the southern cattle tick, Boophilus microplus (Canestrini, 1888) [1; 2] and the dengue vector, the mosquito Aedes aegypti (L.) [3] were functionally and stably expressed in CHO-K1 cells. In order to determine critical kinin residues for the peptide-receptor interaction, kinin core analogs were synthesized as an Ala-replacement series of the peptide FFSWGa and tested by a calcium bioluminescence plate assay. The amino acids Phe1 and Trp4 were essential for activity of the insect kinins in both receptors. It was confirmed that the pentapeptide kinin core is the minimum sequence required for activity and that the C-terminal amide is also essential. The aminoisobutyric acid (Aib)-containing analog, FF[Aib]WGa, was as active as superagonist FFFSWGa on the mosquito receptor in contrast to the tick receptor where it was statistically more active than FFFSWGa by an order of magnitude. This restricted conformation Aib analog provides information on the conformation associated with interaction of the insect kinins with these two receptors. This analog is an important lead in the development of biostable insect kinin analogs for blood-feeders control.

Last Modified: 12/19/2014
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