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

摘要

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) and the dengue vector, the mosquito Aedes aegypti (L.) were functionally and stably expressed in CHO-K1 cells. In order to determine critical kinin residues for the peptidereceptor 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.