SYNTHESIS OF HYALURONIC ACID MIMETICS TO PREVENT METASTASIS

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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. Hyaluronic acid (HA) is a polysaccharide composed of repeating disaccharide units of glucuronic acid and N-acetylglucosamine. It is a component of the extracellular matrix in various mammalian tissues and is also found in the capsular material surrounding certain bacteria, especially pathogenic ones. While it is known to serve as a lubricant and shock absorber, hyaluronic acid has also been shown to be involved in cell signaling. It is this latter function and its role in the metastasis of cancer that we seek to further understand. Results from animal models suggest that a single dose of HA 10-mers will inhibit metastasis for a period of 24-48 hours. One of the main goals of our research will be to increase the length of efficacy by synthesizing S/O-linked mimetics of those HA oligomers. This should render those mimetics less susceptible to hyaluronidase degradation and increase the viability of the agent. Our study will begin with the synthesis of the HA mimetics in which the oxygen in the 1¿ 4 glycosidic bond has been replaced with a sulfur atom. The resulting oligosaccharides will be used to create a dendrimer which will be examined for therapeutic efficacy.