title: The discovery of a novel antagonist - Manduca sexta allatotropin analogue - as an insect midgut active ion transport inhibitor.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, China.
authors: Xi-le
authors: XL
authors: Deng
authors: School of Chemical and Environmental Engineering, Shanghai Institute of Technology, Shanghai, China. kaizp@sit.edu.cn.|Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA. kaizp@sit.edu.cn.
authors: Zhen-Peng
authors: ZP
authors: Kai
authors: Department of Biological Sciences, Ohio University, Athens, OH, USA.
authors: Mary E
authors: ME
authors: Chamberlin
authors: Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA.
authors: Frank M
authors: FM
authors: Horodyski
authors: Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, China. yangxl@cau.edu.cn.
authors: Xin-Ling
authors: XL
authors: Yang
mesh_terms: D000409:Alanine / Q000737:chemistry; D000818:Animals; D004064:Digestive System / Q000378:metabolism; D007301:Insect Hormones / Q000737:chemistry / Q000378:metabolism*; D017136:Ion Transport; D007814:Larva / Q000378:metabolism; D018402:Manduca / Q000254:growth & development / Q000378:metabolism*; D009479:Neuropeptides / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D007301:Insect Hormones; D009479:Neuropeptides; C050669:allatotropin; D000409:Alanine
keywords: active ion transport; allatotropin; analogues; antagonist; structure-activity relationship