The discovery of a novel antagonist - Manduca sexta allatotropin analogue - as an insect midgut active ion transport inhibitor
The discovery of a novel antagonist - Manduca sexta allatotropin analogue - as an insect midgut active ion transport inhibitor
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发现一种新型拮抗剂 - Manduca sexta allatotropin 类似物 - 作为昆虫中肠活性离子转运抑制剂
DOI：
10.1002/ps.4251
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发表时间：
2016-11-01
影响因子：
4.1
通讯作者：
Yang, Xin-ling
中科院分区：
文献类型：
--
作者：
Deng, Xi-le;Kai, Zhen-peng;Yang, Xin-ling
鳞翅目幼虫是农业中的主要害虫，中肠是其营养吸收和离子调节的重要部位。鳞翅目中肠幼虫在过去的几十年里已经成为一种有效的杀虫剂目标。最近的研究表明，一种昆虫神经肽，Manduca sexta allatotropin (Manse-AT)，表现出抑制活性离子运输（AIT）通过幼虫中肠上皮。Manse-AT的AIT抑制能力的充分特性是测定的必要条件。在这项研究中，测定了Manse-AT及其类似物在一定浓度范围内对m.s sexta中肠的AIT抑制作用。通过截断和丙氨酸替代策略研究了Manse-AT的构效关系。结果鉴定出三个残基Thr4、Arg6和Phe8是中肠活性的重要组成部分。替换Glu1、Met2和Met3降低了类似物的效力。用丙氨酸保守取代Gly7对类似物的效力影响不大。我们首次证明了Manse-AT（10-13）在体外对m.s sexta后中肠上皮的活性离子运输具有强效拮抗剂的作用。结论对Manse-AT的结构活性研究有助于开发先导化合物，设计和测试合成的拮抗剂，最终开发出有效的、特异的害虫防治策略。Manse-AT（10-13）是第一个被发现的Manse-AT拮抗剂，与其他昆虫神经肽相比，其作用显著且序列短。它可能是一种潜在的新型害虫防治剂。(c) 2016年化学工业学会
BACKGROUNDThe 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.RESULTSOur 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.CONCLUSIONStructure-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. (c) 2016 Society of Chemical Industry