NMR CHARACTERIZATION OF GALECTIN 3 LIGAND INTERACTIONS

半乳糖凝集素 3 配体相互作用的 NMR 表征

• 批准号: 8361787
• 负责人: JAMES H. PRESTEGARD
• 金额: $ 0.18万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8361787
• 关键词: Anti-Inflammatory Agents; Anti-inflammatory; Antineoplastic Agents; Binding; Carbohydrates; Cells; Chronic; Data; Funding; Galactose; Galectin 3; Grant; Immune; Inflammation; Lanthanoid Series Elements; Ligand Binding; Ligands; Measures; Methodology; National Center for Research Resources; Neoplasm Metastasis; Principal Investigator; Process; Proteins; Protons; Relaxation; Research; Research Infrastructure; Residual state; Resources; Source; United States National Institutes of Health; base; cancer cell; cost; design; inhibitor/antagonist; interest; trafficking

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Galectin-3 is a galactose-binding mammalian protein with suggested involvement in a variety of processes, including introcellular trafficking, cell-cell and cell-matrix interactions, which modulate immune cells in chronic inflammation and metastasis of malignant cells. Therefore, there is substantial interest in structurally characterizing ligand interactions and bound-ligand geometries of galectin-3 as a basis for the design of possible anti-inflammatory and anti-cancer drugs. Standard NMR methodologies, such as those giving inter-proton distance constraints from transferred NOE data, yield some useful results, but numbers of constraints can be small when carbohydrate ligands are involved, and many of these standard methodologies fail when designed inhibitors with high binding constants and slow exchange rates are used. This collaborative project provides additional orientational constraints using new NMR methodology that measures residual dipolar couplings (RDCs), paramagnetic relaxation enhancements (PREs), and pseudo-contact shifts (PCSs) on ligands bound to the perdeuterated and lanthanide tagged carbohydrate recognition domain of galectin-3.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 Galectin-3是一种半乳糖结合的哺乳动物蛋白，建议参与各种过程，包括细胞室内运输，细胞细胞和细胞 - 基质相互作用，这些相互作用调节恶性细胞的慢性炎症和转移中的免疫细胞。因此，在结构上表征galectin-3的配体相互作用和结合结合的几何形状是设计可能的抗炎和抗癌药物的基础。 标准的NMR方法，例如从传输的NOE数据中提供Proton间距离限制的方法，会产生一些有用的结果，但是当涉及碳水化合物配体时，约束数量可能很少，并且当使用具有高结合常数和缓慢汇率速率的抑制剂时，许多标准方法会失败。该协作项目使用新的NMR方法论提供了其他定向约束，该方法可以测量剩余的双极耦合（RDC），顺磁性放松增强（PRES）和伪连接转移（PCSS），绑定到与perdeuterepere的和lanthanide贴标签的carbohydrate carbohydrate dectition Domain-domain-13。