THE CD44:HYALURONAN PROTEIN:CARBOHYDRATE INTERACTION AS A TARGET FOR INVASIVE/M

CD44：透明质酸蛋白：碳水化合物相互作用作为侵袭/M的靶标

• 批准号: 8364296
• 负责人: OLGUN GUVENCH
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8364296
• 关键词: Behavior; Binding; Biomedical Research; CD44 gene; Carbohydrates; Cell Surface Proteins; Complex; Computer-Aided Design; Development; Frequencies; Funding; Future; Grant; High Performance Computing; Hyaluronan; Malignant neoplasm of prostate; Mechanics; Monosaccharides; National Center for Research Resources; Neoplasm Metastasis; Polysaccharides; Potential Energy; Principal Investigator; Property; Protein-Carbohydrate Interaction; Research; Research Infrastructure; Resources; Scanning; Source; Study models; United States National Institutes of Health; cancer cell; cost; inhibitor/antagonist; malignant breast neoplasm; molecular mechanics; quantum; small molecule

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. The reversible non-covalent binding of the cell-surface protein CD44 to the carbohydrate polysaccharide hyaluronan is implicated in the invasive/metastatic behavior of breast and prostate cancer cells. Blocking this protein:carbohydrate interaction therefore presents a potential means of mitigating invasiveness/metastasis in breast and prostate cancer. Toward this end, we propose to perform quantum mechanical studies on the component monosaccharides of hyaluronan and related carbohydrate compounds to develop and validate a molecular-mechanics force field for future modeling studies of the CD44:hyaluronan complex. The quantum mechanical studies will include relaxed potential-energy scans to elucidate the conformational and geometric properties of the compounds and computed vibrational frequencies to aid in the development of molecular mechanics force constant parameters. The proposed quantum mechanical studies of hyaluronan-related molecules represent an important and necessary first step toward eventual computer-aided design of small-molecule inhibitors of the CD44:hyaluronan protein:carbohydrate interaction.

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。 细胞表面蛋白 CD44 与碳水化合物多糖透明质酸的可逆非共价结合与乳腺癌和前列腺癌细胞的侵袭/转移行为有关。因此，阻断这种蛋白质：碳水化合物相互作用是减轻乳腺癌和前列腺癌侵袭/转移的潜在方法。为此，我们建议对透明质酸和相关碳水化合物的单糖成分进行量子力学研究，以开发和验证分子力学力场，用于 CD44:透明质酸复合物的未来建模研究。量子力学研究将包括松弛势能扫描，以阐明化合物的构象和几何特性，并计算振动频率，以帮助开发分子力学力常数参数。拟议的透明质酸相关分子的量子力学研究代表了最终计算机辅助设计 CD44：透明质酸蛋白：碳水化合物相互作用的小分子抑制剂的重要且必要的第一步。