Evaluation of a PK/PBAN analog with an (E)-alkene, trans-Pro isostere identifies the Pro orientation for activity in four diverse PK/PBAN bioassays
Evaluation of a PK/PBAN analog with an (E)-alkene, trans-Pro isostere identifies the Pro orientation for activity in four diverse PK/PBAN bioassays
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DOI：
10.1016/j.peptides.2009.04.017
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发表时间：
2009-07-01
期刊：
影响因子：
3
通讯作者：
Altstein, Miriam
中科院分区：
文献类型：
--
作者：
Nachman, Ronald J.;Wang, Xiaodong J.;Altstein, Miriam
焦激肽/信息素生物合成激活神经肽（PK/PBAN）家族在多种昆虫的一系列重要生理过程中发挥着多功能作用。一种含有(E)-烯烃反式亲等构成分的活性核心类似物在四种不同昆虫的PK/PBAN生物测定中进行了评估。这些生物测定包括：飞蛾Heliothis peltigera的信息素生物合成、沿海夜蛾Spodoptera littoralis幼虫的黑化、bullatia Neobellieria bullata幼虫的化蛹加速以及Leucophaea maderae蟑螂的后肠收缩。在所有四种PK/PBAN生物测定中，构象约束类似物的活性与相同长度的亲本PK/PBAN肽相当，并且在其中三种生物测定中与自然长度的肽活性相匹配或接近。在黑化生物测定中，约束类似物的功效（最大反应）超过天然PBAN1-33的2倍（在1 nmol时）。这些结果为PK/PBAN神经肽在与一系列不同的PK/PBAN生物测定相关的受体相互作用时所采用的Pro取向和核心构象提供了强有力的证据。这项工作进一步确定了一个支架，用它来设计模仿PK/PBAN类似物，作为开发环境有利的害虫管理剂的潜在线索，能够破坏PK/PBAN调节的系统。Elsevier Inc.出版。
The pyrokinin/pheromone biosynthesis activating neuropeptide (PK/PBAN) family plays a multifunctional role in an array of important physiological processes in a variety of insects. An active core analog containing an (E)-alkene, trans-Pro isosteric component was evaluated in four disparate PK/PBAN bioassays in four different insect species. These bioassays include pheromone biosynthesis in the moth Heliothis peltigera, melanization in the larval Spodoptera littoralis, pupariation acceleration in the larval fly Neobellieria bullata, and hindgut contraction in the cockroach Leucophaea maderae. The conformationally constrained analog demonstrated activity equivalent to parent PK/PBAN peptides of equal length in all four PK/PBAN bioassays, and matched and/or approached the activity of peptides of natural length in three of them. In the melanization bioassay, the constrained analog exceeded the efficacy (maximal response) of the natural PBAN1-33 by a factor of 2 (at 1 nmol). The results provide strong evidence for the orientation of Pro and the core conformation adopted by PK/PBAN neuropeptides during interaction with receptors associated with a range of disparate PK/PBAN bioassays. The work further identifies a scaffold with which to design mimetic PK/PBAN analogs as potential leads in the development of environmentally favorable pest management agents capable of disrupting PK/PBAN-regulated systems. Published by Elsevier Inc.