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

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 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细胞和前列腺癌的侵袭/转移行为有关。阻断这种蛋白：因此，碳水化合物的相互作用提供了一种潜在的方法来减轻乳腺癌和前列腺癌的侵袭/转移。为此，我们建议对透明质酸和相关碳水化合物的组成单糖进行量子力学研究，以开发和验证分子力学力场，为未来CD44：透明质酸复合体的模拟研究奠定基础。量子力学研究将包括放松势能扫描，以阐明化合物的构象和几何性质，并计算振动频率，以帮助开发分子力常数参数。拟议的透明质酸相关分子的量子力学研究代表着朝着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迈出了重要而必要的第一步。

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.