Synthesis of U-theraphotoxin-Pv1a_1, an Aedes aegypti larvicidal disulfide bridged peptide from the Colombian tarantula Pamphobeteus verdolaga (Araneae: Theraphosidae)

The attention to the increased resistance of <i>Aedes aegipty</i> to traditional insecticides has been directed to the development of bioinsecticides, such as those produced by insect predators, e.g. spiders. Here we present the solid-phase synthesis of native U-theraphotoxin-Pv1a_1 (n-Pv1a_1) from <i>Pamphobeteus verdolaga</i>, an active (by contact) insecticidal peptide against <i>A. aegipty</i>. U-theraphotoxin-Pv1a_1 sequence was gathered from venom proteomics and venom gland transcriptomics of <i>Pamphobeteus verdolaga</i>, and synthesized by solid phase using the Fmoc strategy followed by dimethyl sulfoxide promoted native disulfide bond formation. The synthetic peptide (s-Pv1a_1) was assayed for larvicidal activity in II and III instar <i>A. aegypti</i> larvae, as well as for cytotoxicity in human red blood and HaCat cells. s-Pv1a_1 showed potent activity towards <i>A</i>. <i>aegypti</i> larvae in the micro molar range, while showing no hemolytic activity and mild cytotoxicity to HaCat cells. Its potent contact activity makes n-Pv1a_1 and its synthetic version, s-Pv1a, promising biopesticides for the control of mosquito populations.