Xie Yong, Zhang Li, Zhang Chuanliang, Wu Xiaoqing, Deng Xile, Yang Xinling, Tobe Stephen S
†Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, People's Republic of China.
‡Department of Cell and Systems Biology, University of Toronto, 25 Harbord Street, Toronto, Ontario M5S 3G5, Canada.
J Agric Food Chem. 2015 Mar 25;63(11):2870-6. doi: 10.1021/acs.jafc.5b00882. Epub 2015 Mar 13.
An allatostatin (AST) neuropeptide mimic (H17) is a potential insect growth regulator, which inhibits the production of juvenile hormone (JH) by the corpora allata. To determine the effect of conformation of novel AST analogues and their ability to inhibit JH biosynthesis, eight insect AST analogues were synthesized using H17 as the lead compound by N-methylation scanning, which is a common strategy for improving the biological properties of peptides. A bioassay using JH production by corpora allata of the cockroach Diploptera punctata indicated that single N-methylation mimics (analogues 1-4) showed more activity than double N-methylation mimics (analogues 5-8). Especially, analogues 1 and 4 showed roughly equivalent activity to that of H17, with IC50 values of 5.17 × 10(-8) and 6.44 × 10(-8) M, respectively. Molecular modeling based on nuclear magnetic resonance data showed that the conformation of analogues 1 and 4 seems to be flexible, whereas analogues 2 and 3 showed a type IV β-turn. This flexible linear conformation was hypothesized to be a new important and indispensable structural element beneficial to the activity of AST mimics.
一种咽侧体抑制素（AST）神经肽模拟物（H17）是一种潜在的昆虫生长调节剂，它可抑制咽侧体产生保幼激素（JH）。为了确定新型AST类似物的构象及其抑制JH生物合成的能力的影响，以H17为先导化合物，通过N-甲基化扫描合成了8种昆虫AST类似物，这是一种改善肽生物学特性的常用策略。利用斑点翅蜚蠊咽侧体产生JH的生物测定表明，单N-甲基化模拟物（类似物1-4）比双N-甲基化模拟物（类似物5-8）表现出更高的活性。特别是，类似物1和4表现出与H17大致相当的活性，IC50值分别为5.17×10（-8）和6.44×10（-8）M。基于核磁共振数据的分子模拟表明，类似物1和4的构象似乎是灵活的，而类似物2和3表现出IV型β-转角。这种灵活的线性构象被认为是对AST模拟物活性有益的一种新的重要且不可或缺的结构元件。
