MAPPING PEPTIDE BINDING SITES OF SP & SK RECEPTORS

SP 肽结合位点图谱

• 批准号: 6123247
• 负责人: NORMAN D BOYD
• 金额: --
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6123247
• 关键词: Mammalia; biological products; biomedical resource; biotechnology; mental disorders; nervous system; pain; proteins; structural biology

The three-dimensional structure of the binding pockets of the SP and SK receptors is being defined with respect to their transmembrane alpha-helices and extracellular domains by determining the sites of covalent attachment of a series of SP and SK derivatives containing the photoreactive amino acid p-benzoylphenylalanine spaced at different positions along the amino acid sequences of the two peptides. For each photoaffinity ligand, the amino acid residues of the binding site that becomes covalently labelled are being determined by microsequencing of purified receptor fragments initially located in the primary sequence with the aid of site-specific antibodies andmass spectrometry. A comparative analysis of the similar and distinctive features of these binding domains should provide insight into the molecular basis of peptide selectivity and receptor activation. A related project is determination of the site of attachment of a tritiated photoreactive azide derivative of the nonpeptide SP antagonist CP-96,345. An understanding of the relationship between the sites for peptide agonists and the nonpeptide antagonist may provide insight into the mechanism of the antagonist effects of this compound, and the information to be gained from the project as a whole may advance the rational design of therapeutic agents for clinical entities in which these peptides participate.

SP的结合口袋的三维结构 和SK受体正在定义其跨膜 通过确定的位置 一系列含有SP和SK衍生物的共价附件 在间隔 沿两个氨基酸序列的不同位置 肽。 对于每个光接触配体， 确定了共价标记的结合位点正在确定 通过对最初位于 借助于位点特异性抗体和质量的主要序列 光谱法。 相似和独特的比较分析 这些绑定域的特征应洞悉 肽选择性和受体激活的分子基础。 一个 相关项目是确定依恋部位 非肽SP的TritiT型光反应性叠氮衍生物 对手CP-96,345。 对关系的理解 肽激动剂和非肽拮抗剂的位点可能 提供有关此拮抗剂作用机制的见解 化合物，以及从整个项目中获得的信息 可以推进临床治疗剂的合理设计 这些肽参与的实体。