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Evaluation of chemical strategies for improving the stability and oral toxicity of insecticidal peptides

Lookup NU author(s): Dr Neil AudsleyORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2018 by the authors. Spider venoms are a rich source of insecticidal peptide toxins. Their development as bioinsecticides has, however, been hampered due to concerns about potential lack of stability and oral bioactivity. We therefore systematically evaluated several synthetic strategies to increase the stability and oral potency of the potent insecticidal spider-venom peptide !-HXTX-Hv1a (Hv1a). Selective chemical replacement of disulfide bridges with diselenide bonds and N- to C-terminal cyclization were anticipated to improve Hv1a resistance to proteolytic digestion, and thereby its activity when delivered orally. We found that native Hv1a is orally active in blowflies, but 91-fold less potent than when administered by injection. Introduction of a single diselenide bond had no effect on the susceptibility to scrambling or the oral activity of Hv1a. N- to C-terminal cyclization of the peptide backbone did not significantly improve the potency of Hv1a when injected into blowflies and it led to a significant decrease in oral activity. We show that this is likely due to a dramatically reduced rate of translocation of cyclic Hv1a across the insect midgut, highlighting the importance of testing bioavailability in addition to toxin stability.

Publication metadata

Author(s): Herzig V, de Araujo AD, Greenwood KP, Chin YK-Y, Windley MJ, Chong Y, Muttenthaler M, Mobli M, Audsley N, Nicholson GM, Alewood PF, King GF

Publication type: Article

Publication status: Published

Journal: Biomedicines

Year: 2018

Volume: 6

Issue: 3

Online publication date: 28/08/2018

Acceptance date: 23/08/2018

Date deposited: 11/11/2019

ISSN (electronic): 2227-9059

Publisher: MDPI AG


DOI: 10.3390/biomedicines6030090


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