Core B, Characterization and Synthesis of Novel Conotoxin Peptides

摘要 在这个旨在发现新的生理学的多学科计划项目(PP)中 重要的多肽配体和扩大我们对多肽作用机制的理解 芋螺毒素--“新型芋螺毒素多肽的表征与合成”核心B具有多重目的 (如下所述)，使其直接或间接从属于所有项目。此外，它还将 将试剂贡献给更广泛的科学界。 这个核心将执行几个关键和独特的活动，包括肽的合成，纯化， 合成肽和天然肽的分析和表征、质谱分析、开发 合成和分析挑战以及发现项目所需的方法学都概述在 具体目标(1-5)。 在室内和高架的固体载体上使用BOC或FMOC策略进行多肽合成 温度。多肽的分析和表征将使用高效液相色谱 毛细管区带电泳法(CZE)、圆二色谱(CD)和质谱学(MS)。 方法学的发展可能包括翻译后新氨基酸的合成或 测试用于层析的新型载体等。质谱学将独立用于 通过犹他州大学进行的提纯步骤，跟踪天然芋螺毒素(约1000) 跑/年)和索尔克研究所合成肽的特性(约500跑/年)。 发现项目将集中于使用原始合成孔径雷达设计选定毒素的类似物 在索尔克公司多年发展起来的方法。对于这些服务中的每一项，高度专业化的设备 训练有素的人员是必不可少的，也是可用的。将这些包括在每个项目中将导致 造成重复劳动，因此效率低下。相比之下，通过将这些工作集中在一个核心中， 通过专业化可以提高生产率。质量控制也可以更一致地和 由核心董事有效监督。 核心将由J.Rivier博士、B.Olivera博士、M.McIntosh博士和W.Fischer博士共同管理。优先次序 将在与应用程序中定义的用户协商后分配。一般来说，先到先得。 服务策略将用于分配优先级。

Summary Within this multi-disciplinary Program Project (PP) directed toward the discovery of novel physiologically important peptide ligands and toward expanding our understanding of the mechanisms of action of peptide conotoxins, the "Characterization and Synthesis of Novel Conotoxin Peptides" Core B has multiple aims (described below) that result in it being subservient directly or indirectly to all Projects. Additionally, it will contribute reagents to the broader scientific community. This Core will carry out several critical and distinct activities consisting of peptide synthesis, purification, analysis and characterization, mass spectrometric analysis of synthetic and native peptides, development of methodologies as required by synthetic and analytical challenges and discovery projects all outlined under Specific Aims (1-5). Peptide synthesis will be done using the Boc or Fmoc strategies on solid supports, at room and elevated temperatures. Peptide analysis and characterization will use high performance liquid chromatography (HPLC), capillary zone electrophoresis (CZE), circular dichroism (CD) and mass spectromety (MS). Methodological developments may include the synthesis of posttranslational novel amino acids or the testing of novel supports for chromatography among others. Mass spectrometry will be used independently to follow native conotoxins through their purification steps carried out at the University of Utah (ca. 1000 runs/year) and characterization of synthetic peptides at the Salk Institute (ca. 500 runs/year). Discovery projects will concentrate on the design of analogs of selected toxins using original SAR approaches developed over many years at Salk. For each of these services, highly specialized equipment and well-trained personnel are essential and available. To include these into each of the Projects would lead to a duplication of effort and thus be inefficient. In contrast, by centralizing these efforts in a Core, productivity can be increased through specialization. Quality control can also be more consistently and efficiently supervised by the Core Directors. The Core will be administered jointly by Drs. J. Rivier, B. Olivera, M. McIntosh and W. Fischer. Priorities will be assigned in consultation with the users as defined in the application. In general, a first come, first served policy will be used to assign priority.