Synthesis and biological activity of FGLamide allatostatin analogs with Phe3 residue modifications

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• 作者：Yong Xie ; Meizi Wang ; Li Zhang ; Xiaoqing Wu ; Xinling Yang and Stephen S. Tobe
• 刊名：Journal of Peptide Science
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：22
• 期：9
• 页码：600-606
• 全文大小：437K
• ISSN：1099-1387

文摘

A FGLamide allatostatin neuropeptide mimic (H17) is a potential insect growth regulator which inhibits the production of juvenile hormone by the corpora allata. To find more evidence to reveal the structure–activity relationships of the Phe³ residue in the C-terminal conserved pentapeptide and search for novel analogs with high activity, a series of Phe³ residue-modified analogs were designed and synthesized using H17 as the lead compound. Bioassay using juvenile hormone (JH) production by corpora allata of the cockroach Diploptera punctata indicated that analogs 4, 11, and 13 showed strong ability to inhibit JH production in vitro, with IC₅₀ of 38.5, 22.5, and 26 nM, respectively. As well, the activity of analog 2 (IC₅₀: 89.5 nM) proved roughly equivalent to that of H17. Based on the primary structure–activity relationships of Phe³ residue, we suggest that for analogs containing six-membered aromatic rings, removing the methylene group of Phe³ or an o-halogen or p-halogen-substituted benzene ring could increase the ability to inhibit biosynthesis of JH. This study will be useful for the design of new allatostatin analogs for insect management. Copyright