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Synthesis, Biological Activity, and Conformational Study of N-Methylated Allatostatin Analogues Inhibiting Juvenile Hormone Biosynthesis

Xie, Yong, Zhang, Li, Zhang, Chuanliang, Wu, Xiaoqing, Deng, Xile, Yang, Xinling, Tobe, Stephen S.
Journal of agricultural and food chemistry 2015 v.63 no.11 pp. 2870-2876
Diploptera punctata, allatostatin, bioactive properties, bioassays, biosynthesis, corpora allata, inhibitory concentration 50, insect growth regulators, insects, juvenile hormones, molecular models, nuclear magnetic resonance spectroscopy
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.