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The discovery of a novel antagonist – Manduca sexta allatotropin analogue – as an insect midgut active ion transport inhibitor
Author(s) -
Deng Xile,
Kai Zhenpeng,
Chamberlin Mary E,
Horodyski Frank M,
Yang Xinling
Publication year - 2016
Publication title -
pest management science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.296
H-Index - 125
eISSN - 1526-4998
pISSN - 1526-498X
DOI - 10.1002/ps.4251
Subject(s) - manduca sexta , midgut , biology , manduca , insect , antagonist , neuropeptide , sphingidae , medicine , biochemistry , endocrinology , pharmacology , larva , botany , receptor
BACKGROUND The midgut is an important site for both nutrient absorption and ionic regulation in lepidopteran larvae, major pests in agriculture. The larval lepidopteran midgut has become a potent insecticide target over the past few decades. Recent studies have shown that an insect neuropeptide, Manduca sexta allatotropin (Manse‐ AT ), exhibits inhibition of active ion transport ( AIT ) across the larval midgut epithelium. The full characteristic of the AIT inhibition capacity of Manse‐ AT is essential to assay. In this study, AIT inhibition across the M. sexta midgut by Manse‐ AT and its analogues in a range of concentrations was assayed. The structure–activity relationship of Manse‐ AT was also studied by truncated and alanine‐replacement strategies. RESULTS Our results identified three residues, Thr4, Arg6 and Phe8, as the most important components for activity on the midgut. Replacement of Glu1, Met2 and Met3 reduced the potency of the analogues. The conservative substitution of Gly7 with alanine had little effect on the potency of the analogues. We demonstrated for the first time that Manse‐ AT (10–13) behaves as a potent antagonist in vitro on active ion transport across the epithelium of the posterior midgut in M. sexta . CONCLUSION Structure–activity studies of Manse‐ AT are useful in developing lead compounds for the design and testing of synthetic antagonists, ultimately to develop potent and specific pest control strategies. Manse‐ AT (10–13) has been discovered as the first Manse‐ AT antagonist, with a significant effect and a short sequence compared with other insect neuropeptides. It may be a new potential pest control agent in the future. © 2016 Society of Chemical Industry