Peptidomimetics in the discovery of new insect growth regulators: studies on the structure-activity relationships of the core pentapeptide region of allatostatins.
Peptidomimetics in the discovery of new insect growth regulators: studies on the structure-activity relationships of the core pentapeptide region of allatostatins.
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DOI：
10.1021/jf200085d
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发表时间：
2011-02
影响因子：
6.1
通讯作者：
Zhenpeng Kai;Yong Xie;Juan Huang;S. Tobe;Jinrui Zhang;Yun Ling;Li Zhang;Yi-chen Zhao;Xinling Yang
中科院分区：
文献类型：
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作者：
Zhenpeng Kai;Yong Xie;Juan Huang;S. Tobe;Jinrui Zhang;Yun Ling;Li Zhang;Yi-chen Zhao;Xinling Yang
蟑螂型allatostatin（ASTs）是通过抑制蟑螂咽侧体（CA）产生保幼激素而在蟑螂体内发现的。AST被认为是潜在的昆虫生长调节剂（IGR）的候选人，但一些缺点，包括缺乏在体内的效果和在体内的快速降解，排除了它们在害虫管理中的应用。以CA为靶点，以核心五肽区（YDFGL）为前导序列，寻找基于allatostatin的IGR。我们设计并合成了24个类似物，它们模拟了核心区的每个氨基酸，以确定结构-活性关系以及在保留活性的同时缩短核心区的AST的可能性。结果表明，序列FGLa比Y/FX更重要，因为Y/FX模拟物在体外和体内显示出强烈的作用。特别地，化合物I3是通过用6-苯基己酸取代Y/FX合成的，并且表现出比完整核心区域更高的体外活性。此外，化合物I3在体内对斑点双翅夜蛾雌性的保幼激素（JH）生物合成具有明显的作用，为蟑螂管理提供了可能的应用。根据五肽类似物的构效关系，提出了具有潜在活性的AST类似物的一般结构。在我们的研究中展示了一种新的方法，使用肽模拟物在IGRs的发现。
Cockroach-type allatostatins (ASTs) were discovered in cockroaches through their capacity to inhibit the production of juvenile hormone by the corpora allata (CA). ASTs were considered as potential insect growth regulator (IGR) candidates, but several disadvantages, including the absence of the effect in vivo and rapid degradation in vivo, precluded their application in pest management. The CA were selected as the target, and the core pentapeptide region (YDFGL) was chosen as the lead sequence in the search for new IGRs based on the allatostatins. We designed and synthesized 24 analogues, which mimicked each amino acid of the core region, to determine structure-activity relationships and the possibility of shortening the ASTs in the core region while retaining activity. The results suggest that the sequence FGLa is more important than Y/FX because Y/FX mimics show strong effects in vitro and in vivo. In particular, compound I3 was synthesized by substitution of Y/FX with 6-phenylhexnoic acid and exhibits higher activity in vitro than the complete core region. Furthermore, compound I3 has a clear effect in vivo on juvenile hormone (JH) biosynthesis of Diploptera punctata females, providing a possible application for cockroach management. On the basis of the structure-activity relationship of pentapeptide analogues, a general structure of potential potent AST analogues is proposed here. A new approach using peptidomimetics in the discovery of IGRs is demonstrated in our study.