CONUS PEPTIDES AND THEIR RECEPTOR TARGETS

圆锥肽及其受体靶标

• 批准号: 6490055
• 负责人: BALDOMERO M OLIVERA
• 金额: $ 103.42万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6490055
• 关键词: Gastropoda; animal poison; calcium channel blockers; conotoxin; neuropeptide receptor

The five hundred species of cone snails produce small, conformationally constrained peptides in their venoms which generally target receptors and ion channels in the nervous system. The many tens-of- thousands of different Conus peptides are generated by only a few superfamilies, and are organized within each venom into groups of peptides which act synergistically for a common physiological objective. One general goal of this program is the continuing identification and characterization of Conus peptides which target novel receptor and ion channel subtypes. However, another major goal is to understand the underlying principles of molecular recognition and drug development that the cone snails have evolved. The program is organized into a venom resource core, a peptide chemistry core and an electrophysiological core. These cores also directly support "discovery cores" that are exploratory and/or collaborative on Conus peptides which are not directly supported as projects. Three major projects comprise the program. The goal of the first project is to understand the underlying design of Conus peptides that allow them to discriminate between closely related target receptors. The standard features of Conus peptides which confer target selectively will be identified. The second project focuses on a few fish-hunting Conus venoms; the goal is to understand in mechanistic detail how efficient prey capture is achieved by elucidating the role of each individual Conus peptide, and evaluating the synergy between groups of peptides. Finally, the third project investigates the genetic basis of Conus peptide hypervariability, and in addition characterize the enzymatic basis of an unusual post-translational modification, the gamma-carboxylation of glutamate residues.

五百种锥形蜗牛会产生小的， 毒液中构象约束的肽通常 神经系统中的目标受体和离子通道。数十个 数千种不同的圆锥形肽仅由少量产生 超家族，在每个毒液中组织成一组肽 对于共同的生理目标而言，这是协同作用的。一 该计划的一般目标是持续识别和 靶向新型受体和离子的圆锥肽的表征 通道亚型。但是，另一个主要目标是了解 分子识别和药物开发的基本原则 锥蜗牛已经发展。 该程序被组织成毒液资源核心，肽 化学核心和电生理核心。这些芯也直接 支持探索性和/或协作的“发现核心” 不直接支持项目的圆锥形肽。 三个主要项目包括该计划。第一个目标 项目是要了解圆锥肽的基础设计 允许他们区分密切相关的目标受体。这 圆锥肽的标准特征选择性地授予目标 被识别。第二个项目着重于一些猎鱼圆锥 毒液；目的是了解机械详细信息有效的猎物 捕获是通过阐明每个单个圆锥的作用来实现的 肽，并评估肽组之间的协同作用。最后， 第三个项目研究圆锥肽的遗传基础 过度变化，此外，还表征了 不寻常的翻译后修饰，伽马羧化的 谷氨酸残留物。