Identification of selective and non-selective, biostable β-amino acid agonists of recombinant insect kinin receptors from the southern cattle tick Boophilus microplus and mosquito Aedes aegypti

Abstract The multifunctional arthropod ‘insect kinins’ share the evolutionarily conserved C-terminal pentapeptide motif Phe-X 1 -X 2 -Trp-Gly-NH 2 , where X 1  = His, Asn, Ser, or Tyr and X 2  = Ser, Pro, or Ala. Eight different analogs of the insect kinin C-terminal pentapeptide active core in which the critical residues Phe 1 , Pro 3 and Trp 4 are replaced with β 3 -amino acid and/or their β 2 -amino acid counterparts were evaluated on recombinant insect kinin receptors from the southern cattle tick, Boophilus microplus (Canestrini) and the dengue vector, the mosquito Aedes aegypti (L.). A number of these analogs previously demonstrated enhanced resistance to degradation by peptidases. Single-replacement analog β 2 Trp 4 and double-replacement analog [β 3 Phe 2 , β 3 Pro 3 ] of the insect kinins proved to be selective agonists for the tick receptor, whereas single-replacement analog β 3 Pro 3 and double-replacement analog [β 3 Phe, β 3 Pro 3 ] were strong agonists on both mosquito and tick receptors. These biostable analogs represent new tools for arthropod endocrinologists and potential leads in the development of selective, environmentally friendly arthropod pest control agents capable of disrupting insect kinin-regulated processes.