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.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 半乳糖凝集素-3是一种半乳糖结合的哺乳动物蛋白，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，其调节慢性炎症和恶性细胞转移中的免疫细胞。因此，在结构上表征半乳糖凝集素-3的配体相互作用和结合的配体几何形状作为设计可能的抗炎和抗癌药物的基础方面存在很大的兴趣。 标准的核磁共振方法，例如那些从传输的NOE数据中给出质子间距离约束的方法，产生了一些有用的结果，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和低结合常数的抑制剂时，许多这些标准方法都会失败。使用交换速率。这个合作项目提供了额外的取向限制，使用新的NMR方法，测量残留偶极耦合（RDC），顺磁弛豫增强（PRE），和伪接触位移（PCS）的配体结合到全氘和镧系元素标记的碳水化合物识别结构域的半乳糖凝集素-3。