NOVEL NEUROACTIVE PEPTIDES FROM CONUS

来自 Conus 的新型神经活​​性肽

• 批准号: 3413442
• 负责人: LOURDES J CRUZ
• 金额: $ 13.07万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-17 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3413442
• 关键词: Gastropoda; NMDA receptors; RNA; genetic library; inhibitor /antagonist; laboratory mouse; molecular cloning; molecular genetics; neurotoxins; peptide structure; peptides; protein purification; radionuclides; receptor binding; synthetic peptide; transposon /insertion element

The major goal of this project is to develop new ligands for receptors and ion channels using biologically active peptides from two cone snail venoms, Conus textile and Conus radiatus. Our interest in Conus radiatus venom is in peptide probes which have NMDA antagonist activity; preliminary data suggest five candidate peptides. We are carrying out an extensive characterization of biologically active peptides in Conus textile venom because we feel that many of these will serve as useful molecular probes for key invertebrate nervous systems. Initially, two novel peptides in Conus textile venom that elicit specific behavioral symptoms analogous to the behavior of mutant mice deficient in glycine receptors. The second is the "King-Kong" peptide which makes lobsters assume a dominant posture even in the presence of bigger lobsters. Both peptides are 27 amino acids long and contain 6 residues of cysteine. Peptide will be chemically synthesized and the physiological activity of each peptide will be examined. Radiolabeled derivatives of the peptides will be made and used as probes for their receptor targets. Recently, cDNA clones of the King-Kong peptide were isolated. However, of 15 clones sequenced, a family of transcripts encoding three different propeptides was revealed. When the three propeptide sequences are aligned, highly conserved and hypervariable regions can be defined. The N-terminal excised region and the 6 cysteine residues in the final peptide comprise the constant region; the intercysteine segments are the hypervariable regions. We will test whether an N-terminal excised region can be correlated to the disulfide bonded framework of a Conus peptide. The combination of biochemical and cloning techniques provides a powerful tool for the analysis of peptides from Conus venom, and their development as tools in neurobiology.

该项目的主要目的是开发新的配体，用于受体和 使用来自两个锥蜗牛毒液的生物活性肽的离子通道， 圆锥形纺织品和圆锥形辐射。 我们对Conus辐射毒液的兴趣是 在具有NMDA拮抗剂活性的肽探针中；初步数据 建议五个候选肽。 我们正在进行广泛的 圆锥纺织毒液中生物活性肽的表征 因为我们认为其中许多将用作有用的分子探针 对于关键的无脊椎动物神经系统。 最初，有两个新型肽 引起类似于类似的特定行为症状的圆锥纺织毒液 突变小鼠缺乏甘氨酸受体的行为。 第二个是 使龙虾的“王子”肽甚至是占主导地位的姿势 在大型龙虾面前。 这两种肽均为27个氨基酸长 并含有6种半胱氨酸的残留物。 肽将化学合成 并将检查每种肽的生理活性。 将制作并用作肽的放射性标记的衍生物 对于他们的受体靶标。 最近，分离了金刚肽的cDNA克隆。 但是， 15个克隆测序，一个编码三种不同的成绩单家族 暴露于丙肽。 当三个前肽序列对齐时， 可以定义高度保守和高变量区域。 N末端 最终肽中的切除区域和6个半胱氨酸残基包括 恒定区域；囊肿间段是高变量的 地区。 我们将测试是否可以 与圆锥肽的二硫键键合框架相关。 这 生化技术和克隆技术的结合提供了强大的工具 为了分析来自conus毒液的肽及其发育 神经生物学的工具。