The overall objective of this project is to develop polysulfated carbohydrate derivatives that will inhibit the action of fibroblast growth factors (FGF). FGF's have been implicated in several human cancers both as angiogenic factors and as growth factors capable of sustaining autonomous cell proliferation. Inhibition of these growth factors could inhibit tumor growth. The current proposal is based on the preliminary observations that polysulfated carbohydrate derivatives such as pentosan polysulfate and polysulfated aromatic compounds such as suramin inhibit FGF activity and suppress the growth of cancer cells, and that heparin-like molecules are required for FGF activity. Specifically, we propose to synthesize related compounds from maltotetrose and cellotetrose with FGF inhibitory activity. Since they are based on natural products, they may have fewer side affects than compounds such as suramin. The advantages of these compounds for clinical use would include ease of administration and chemical homogeneity.
