Biostable β-amino acid PK/PBAN analogs: Agonist and antagonist properties
Biostable β-amino acid PK/PBAN analogs: Agonist and antagonist properties
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DOI：
10.1016/j.peptides.2008.11.007
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发表时间：
2009-03-01
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.;Ben Aziz, Orna;Altstein, Miriam
焦激肽/信息素生物合成激活神经肽(PK/PBAN)家族在昆虫的一系列重要生理过程中发挥着重要作用。合成了含有P-氨基酸的PK/PBAN类似物，并对其进行了信息素测定、斜纹夜蛾的嗜黑试验、新麦长管虫的化蛹试验和乳白粉虫的后肠收缩试验。两个类似物(PK-βA-1和PK-βA-4)显示出极大地增强了对奈普利辛和血管紧张素转换酶的抵抗力，这两种酶被证明能降解天然多肽。尽管PK核心发生了变化，但在所有四种生物检测中，类似的PK-βA-4都代表着一种生物稳定的、非选择性的激动剂，基本上与天然PK在羽化实验中的效力相当。类似物PK-βA-2在促黑试验中是一种有效的激动剂，在1pmol时完全有效。在某些情况下，给予类似物的结构变化会改变生理反应。在所有四种生物测定中，类似物PK-βA-3都是非选择性激动剂。类似物PK-βA-1比亲本PK多肽显示出更高的选择性；它在化蛹实验中几乎没有活性，在信息素和黑色素亲和性分析中是一种生物稳定的拮抗剂，没有亲本六肽的显著激动性。这些类似物在某些情况下为内分泌学家提供了新的生物稳定工具，用于研究PK/PBAN介导的各种生理过程机制的异同。它们还可能在开发以PK/PBAN为基础的、针对昆虫的害虫管理剂方面提供线索。(C)2008 Elsevier Inc.保留所有权利。
The pyrokinin/pheromone biosynthesis activating neuropeptide (PK/PBAN) family plays a significant role in a multifunctional array of important physiological processes in insects. PK/PBAN analogs incorporating P-amino acids were synthesized and evaluated in a pheromonotropic assay in Heliothis peltigera, a melanotropic assay in Spodoptera littoralis, a pupariation assay in Neoliellieria bullata, and a hindgut contractile assay in Leucophaea maderae. Two analogs (PK-beta A-1 and PK-beta A-4) demonstrate greatly enhanced resistance to the peptidases neprilysin and angiotensin converting enzyme that are shown to degrade the natural peptides. Despite the changes to the PK core, analog PK-beta A-4 represents a biostable, non-selective agonist in all four bioassays, essentially matching the potency of a natural PK in pupariation assay. Analog PK-beta A-2 is a potent agonist in the melanotropic assay, demonstrating full efficacy at 1 pmol. In some cases, the structural changes imparted to the analogs modify the physiological responses. Analog PK-beta A-3 is a non-selective agonist in all four bioassays. The analog PK-beta A-1 shows greater selectivity than parent PK peptides; it is virtually inactive in the pupariation assay and represents a biostable antagonist in the pheromonotropic and melanotropic assays, without the significant agonism of the Parent hexapeptide. These analogs provide new, and in some cases, biostable tools to endocrinologists studying similarities and differences in the mechanisms of the variety of PK/PBAN mediated physiological processes. They also may provide leads in the development of PK/PBAN-based, insect-specific pest management agents. (c) 2008 Elsevier Inc. All rights reserved.