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.
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