Evaluation of Chemical Strategies for Improving the Stability and Oral Toxicity of Insecticidal Peptides

摘要: Spider venoms are a rich source of insecticidal peptide toxins. Their development as bioinsecticides has, however, been hampered due to concerns about potential lack stability and oral bioactivity. We therefore systematically evaluated several synthetic strategies increase the potency potent spider-venom ω-HXTX-Hv1a (Hv1a). Selective chemical replacement disulfide bridges with diselenide bonds N- C-terminal cyclization were anticipated improve Hv1a resistance proteolytic digestion, thereby its activity when delivered orally. found that native is orally active in blowflies, but 91-fold less than administered by injection. Introduction single bond had no effect on susceptibility scrambling or Hv1a. backbone did not significantly injected into blowflies it led significant decrease activity. show this likely dramatically reduced rate translocation cyclic across insect midgut, highlighting importance testing bioavailability addition toxin stability.