Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, People's Republic of China.
J Agric Food Chem. 2010 Mar 10;58(5):2652-8. doi: 10.1021/jf902156k.
Cockroach-type allatostatins (FGLamides) (ASTs) can inhibit the production of juvenile hormone in vitro, and they therefore are regarded as possible insect growth regulator (IGR) candidates for pest control. However, several shortcomings, such as the absence of in vivo effects, rapid degradation, and high production costs, preclude their practical use in pest management. To discover new IGRs, 25 novel analogues of pentapeptide (Y/FXFGLa) were designed and synthesized with different aromatic acids, fatty acids, and dicarboxylic acids as the Y/FX region replacements on the basis of previous results. Their bioactivities in vitro were determined, and the results showed that eight analogues (K14, K15, K17, K18, K19, K23, K24, and K25) were more active than the lead, core region pentapeptide. The IC(50) values of K15 and K24 (IC(50) = 1.79 and 5.32 nM, respectively) were even lower than that of the natural AST, Dippu-AST 1(IC(50) = 8 nM), which indicated both analogues have better activity than Dippu-AST 1; particularly, K15 has better activity than most natural Dippu-ASTs. A predictable and statistically meaningful hologram quantitative structure-activity relationship (HQSAR) model of 32 AST analogues (28 as training sets and 4 as test sets) was obtained. The final model suggested that a potent AST analogue should contain an aromatic group, a linker of appropriate length, and the FGLa portion. These results will be useful in the design of new AST analogues that are structurally related to the training set compounds.
蜚蠊型保幼激素抑制素（FGLamides）（ASTs）可以在体外抑制保幼激素的产生，因此被认为是潜在的昆虫生长调节剂（IGR）候选物质，可用于害虫防治。然而，由于缺乏体内效应、快速降解和高生产成本等几个缺点，它们在害虫管理中的实际应用受到限制。为了发现新的 IGRs，我们在以前的研究结果基础上，用不同的芳香酸、脂肪酸和二羧酸作为 Y/FX 区域的取代物，设计并合成了 25 种新型五肽（Y/FXFGLa）类似物。我们测定了它们的体外生物活性，结果表明，有 8 种类似物（K14、K15、K17、K18、K19、K23、K24 和 K25）比先导核心区五肽更具活性。K15 和 K24 的 IC50 值（分别为 1.79 和 5.32 nM）甚至低于天然 AST Dippu-AST 1（IC50 值为 8 nM），这表明这两种类似物的活性均优于 Dippu-AST 1；特别是，K15 的活性优于大多数天然的 Dippu-AST。我们得到了 32 种 AST 类似物（28 个作为训练集，4 个作为测试集）的可预测且具有统计学意义的全息定量构效关系（HQSAR）模型。最终模型表明，一个有效的 AST 类似物应该包含一个芳香基团、一个适当长度的连接体和 FGLa 部分。这些结果将有助于设计与训练集化合物在结构上相关的新型 AST 类似物。
