Core B, Characterization and Synthesis of Novel Conotoxin Peptides

核心B，新型芋螺毒素肽的表征与合成

• 批准号: 9334235
• 负责人: JEAN E RIVIER
• 金额: $ 23.36万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9334235
• 关键词: Acids; Alanine; Amino Acids; Applied Research; Basic Science; Biological; Blood capillaries; Chemicals; Chromatography; Circular Dichroism; Communities; Conotoxin; Consultations; Conus Venom; Conus genus; Detection; Development; Digestion; Disulfides; Electrophoresis; Electrospray Ionization; Electrostatics; Equipment; Feedback; Fourier Transform; Freedom; Goals; High Pressure Liquid Chromatography; Human Resources; Hybrids; Hydrolysis; Hydrophobicity; In Situ; Individual; Institutes; Ion Exchange; Ions; Label; Laboratories; Lactams; Lead; Ligands; Mass Spectrum Analysis; Methionine; Methodology; Norleucine; Peptide Synthesis; Peptides; Periodicity; Pharmacology; Phase; Physiological; Policies; Post-Translational Protein Processing; Productivity; Protocols documentation; Quality Control; Reagent; Recovery; Research Personnel; Resolution; Running; S Phase; Scanning; Services; Solid; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Structure-Activity Relationship; Supervision; System; Techniques; Temperature; Testing; Toxin; Training; Universities; Utah; Venoms; analog; capillary; design; experimental study; improved; instrument; interest; member; microwave electromagnetic radiation; milligram; multidisciplinary; novel; programs; receptor; scaffold; synthetic peptide; tool; unnatural amino acids

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.

总结 在这个多学科计划项目（PP）中，旨在发现新的生理学 重要的肽配体，并扩大我们对肽的作用机制的理解 芋螺毒素，“新型芋螺毒素肽的表征和合成”核心B具有多个目的 （如下所述）导致其直接或间接从属于所有项目。此外，它将 为更广泛的科学界贡献试剂。 该核心将进行几个关键和不同的活动，包括肽合成，纯化， 分析和表征，合成和天然肽的质谱分析， 综合和分析挑战以及发现项目所要求的方法， 具体目标（1-5）。 肽合成将使用Boc或Fmoc策略在固体支持物上在室温和高温下进行。 温度肽分析和表征将使用高效液相色谱法 高效液相色谱法（HPLC）、毛细管区带电泳（CZE）、圆二色谱（CD）和质谱（MS）。 方法学的发展可能包括翻译后新氨基酸的合成或 用于色谱的新型载体的测试等。质谱法将独立用于 遵循天然芋螺毒素，通过在犹他州大学（ca. 1000 运行/年）和Salk研究所合成肽的表征（约. 500次/年）。 发现项目将集中于使用原始SAR设计选定毒素的类似物 在索尔克发展多年的方法。对于这些服务，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。将这些纳入每个项目将导致 重复劳动，效率低下。相反，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力。质量控制也可以更加一致， 由核心董事有效监督。 核心研究将由Dr. J. Rivier，B联合给药。Olivera，M. McIntosh和W.费舍尔优先事项 将在与用户协商后分配，如应用程序中所定义。一般来说，先到先得 服务策略将用于分配优先级。