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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 Galectin-3 是一种半乳糖结合哺乳动物蛋白，可能参与多种过程，包括细胞内运输、细胞-细胞和细胞-基质相互作用，在慢性炎症和恶性细胞转移中调节免疫细胞。因此，人们对半乳糖凝集素 3 的配体相互作用和结合配体几何形状的结构表征非常感兴趣，作为设计可能的抗炎和抗癌药物的基础。 标准 NMR 方法，例如从转移的 NOE 数据中给出质子间距离约束的方法，会产生一些有用的结果，但当涉及碳水化合物配体时，约束的数量可能很小，并且当设计具有高结合常数的抑制剂时，许多标准方法会失败并且使用缓慢的汇率。该合作项目使用新的 NMR 方法提供了额外的方向约束，该方法测量与半乳糖凝集素的全氘化和镧系元素标记的碳水化合物识别域结合的配体上的残余偶极耦合 (RDC)、顺磁弛豫增强 (PRE) 和伪接触位移 (PCS)。 3.