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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 细胞表面蛋白CD 44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/转移的潜在手段。为此，我们建议对透明质酸和相关碳水化合物的单糖组分进行量子力学研究，以开发和验证CD 44：透明质酸复合物未来建模研究的分子力学力场。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，以帮助发展分子力学力常数参数。建议透明质酸相关分子的量子力学研究代表了重要的和必要的第一步，最终的计算机辅助设计的小分子抑制剂的CD 44：透明质酸蛋白质：碳水化合物的相互作用。

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.