PDF(Pubmed)
Abstract：
Polyamines (PAs) are polycationic biogenic amines ubiquitously present in all life forms and are involved in molecular signaling and interaction, determining cell fate (e.g., cell proliferation, dif-ferentiation, and apoptosis). The intricate balance in the PAs\' levels in the tissues will determine whether beneficial or detrimental effects will affect homeostasis. It\'s crucial to note that endoge-nous polyamines, like spermine and spermidine, play a pivotal role in our understanding of neu-rological disorders as they interact with membrane receptors and ion channels, modulating neuro-transmission. In spiders and wasps, monoamines (histamine, dopamine, serotonin, tryptamine) and polyamines (spermine, spermidine, acyl polyamines) comprise, with peptides and other sub-stances, the low molecular weight fraction of the venom. Acylpolyamines are venom components exclusively from spiders and a species of solitary wasp, which cause inhibition chiefly of iono-tropic glutamate receptors (AMPA, NMDA, and KA iGluRs) and nicotinic acetylcholine receptors (nAChRs). The first venom acylpolyamines ever discovered (argiopines, Joro and Nephila toxins, and philanthotoxins) have provided templates for the design and synthesis of numerous analogs. Thus far, analogs with high potency exert their effect at nanomolar concentrations, with high se-lectivity toward their ionotropic and ligand receptors. These potent and selective acylpolyamine analogs can serve biomedical purposes and pest control management. The structural modification of acylpolyamine with photolabile and fluorescent groups converted these venom toxins into use-ful molecular probes to discriminate iGluRs and nAchRs in cell populations. In various cases, the linear polyamines, like spermine and spermidine, constituting venom acyl polyamine backbones, have served as cargoes to deliver active molecules via a polyamine uptake system on diseased cells for targeted therapy. In this review, we examined examples of biogenic amines that play an essential role in neural homeostasis and cell signaling, contributing to human health and disease outcomes, which can be present in the venom of arachnids and hymenopterans. With an empha-sis on the spider and wasp venom acylpolyamines, we focused on the origin, structure, derivatiza-tion, and biomedical and biotechnological application of these pharmacologically attractive, chemically modular venom components.
摘要：
多胺（PAs）是普遍存在于所有生命形式中的聚阳离子生物胺，参与分子信号和相互作用。确定细胞命运(例如，细胞增殖，区分，和凋亡）。组织中PAs水平的复杂平衡将决定是否有益或有害影响会影响稳态。重要的是要注意内聚多胺，像精胺和亚精胺,在我们对神经系统疾病的理解中起着关键作用，因为它们与膜受体和离子通道相互作用，调节神经传递.在蜘蛛和黄蜂中，单胺（组胺，多巴胺,血清素,色胺)和多胺(精胺，亚精胺,酰基多胺)包括，肽和其他物质，毒液的低分子量部分。酰基多胺是仅来自蜘蛛和一种孤立黄蜂的毒液成分，主要抑制亲离子性谷氨酸受体(AMPA，NMDA,和KAiGluRs）和烟碱乙酰胆碱受体（nAChRs）。有史以来发现的第一个毒液酰基多胺(精氨酸，Joro和Nephila毒素,和博爱毒素）为许多类似物的设计和合成提供了模板。到目前为止,具有高效力的类似物在纳摩尔浓度下发挥其作用，对它们的离子型和配体受体具有高度的选择性。这些有效和选择性的酰基多胺类似物可以用于生物医学目的和害虫控制管理。用光不稳定基团和荧光基团对酰基多胺进行结构修饰，将这些毒液毒素转化为有用的分子探针，以区分细胞群中的iGluR和nAchR。在各种情况下,线性多胺，像精胺和亚精胺,构成毒液酰基多胺骨架，作为货物通过多胺摄取系统在病变细胞上递送活性分子用于靶向治疗。在这次审查中,我们研究了在神经稳态和细胞信号传导中起重要作用的生物胺的例子，有助于人类健康和疾病的结果，可能存在于蜘蛛和膜翅目昆虫的毒液中。在蜘蛛和黄蜂的毒液上加上酰基多胺，我们专注于起源，结构,衍生工具，以及生物医学和生物技术的应用，化学模块化毒液成分。
