-Conotoxins 是对烟碱的醋胆素受体(nAChRs ) 的特定的子类型作为有势力和选择对手起作用的小抑制二硫化物的肽。我们以前从食虫的 Conus leopardus 从 molluscivorous Conus marmoreus 和 Lp1.4 克隆二 -conotoxins, Mr1.1。他们俩有 -conotoxins 的亚科的典型 4/7-type 框架 neuronal nAChRs 上的那行为。在这个工作,我们化学上综合了这二毒素并且描绘了他们的功能的性质。合成 Mr1.1 能首先禁止唤起的醋胆素(ACh ) 水流 reversibly 在表示卵母细胞的老鼠 7 nAChR,而 Lp1.4 是老鼠的意外特定的 blocker 胎儿的肌肉 11 受体。尽管他们的抑制亲密关系是相对低的,他们的唯一的受体识别侧面为毒素受体相互作用研究使他们成为珍贵工具。Mr1.1 能也压制煽动性的反应在 vivo 伤害,建议它应该进一步关于它在为疼痛的治疗的痛觉缺失和它的机制或治疗学的目标的分子的角色被调查。
α-Conotoxins are small disulfide-constrained peptides that act as potent and selective antagonists on specific subtypes of nicotinic acetylcholine receptors (nAChRs). We previously cloned two α-conotoxins, Mrl.1 from the molluscivorous Conus marmoreus and Lpl.4 from the vermivorous Conus leopardus. Both of them have the typical 4/7-type framework of the subfamily of α-conotoxins that act on neuronal nAChRs. In this work, we chemically synthesized these two toxins and characterized their functional properties. The synthetic Mrl.1 could primarily inhibit acetylcholine (ACh)-evoked currents reversibly in the oocyte-expressed rat α7 nAChR, whereas Lpl.4 was an unexpected specific blocker of the mouse fetal muscle α1β1γδ receptor. Although their inhibition affinities were relatively low, their unique receptor recognition profiles make them valuable tools for toxin-receptor interaction studies. Mr1.1 could also suppress the inflammatory response to pain in vivo, suggesting that it should be further investigated with respect to its molecular role in analgesia and its mechanism or therapeutic target for the treatment of pain.