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: 8171912
• 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: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171912
• 关键词: Behavior; Binding; Breast; CD44 gene; Carbohydrates; Cell Surface Proteins; Complex; Computer Retrieval of Information on Scientific Projects Database; Computer-Aided Design; Development; Frequencies; Funding; Future; Grant; Hyaluronan; Institution; Malignant neoplasm of prostate; Mechanics; Monosaccharides; Neoplasm Metastasis; Polysaccharides; Potential Energy; Property; Protein-Carbohydrate Interaction; Research; Research Personnel; Resources; Scanning; Source; Study models; United States National Institutes of Health; cancer cell; inhibitor/antagonist; 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. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 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浸润性/转移性行为有关。因此，阻止这种蛋白质：碳水化合物的相互作用提出了降低乳腺癌和前列腺癌中侵入性/转移的潜在手段。为此，我们建议对透明质酸和相关碳水化合物化合物的成分单糖进行量子力学研究，以开发和验证分子力学力场，以对CD44：透明质酸综合体进行未来的建模研究。量子力学研究将包括松弛的电位能量扫描，以阐明化合物和计算的振动频率的构象和几何特性，以帮助开发分子力学力量恒定参数。介绍的透明质酸相关分子的量子力学研究代表了CD44的小分子抑制剂最终的计算机辅助设计：透明质酸蛋白：碳水化合物相互作用的重要第一步。