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Metalloglycomics: Investigating The Interactions Of Metal Complexes With Heparan Mimetics, Wyatt Johnson
Metalloglycomics: Investigating The Interactions Of Metal Complexes With Heparan Mimetics, Wyatt Johnson
Theses and Dissertations
Proteoglycans containing Heparan Sulfate (HS), a sulfated glycosaminoglycan (GAG), play a major role in the cell signaling process, interacting with many different proteins. HS is over expressed on the surface of many cancer cells. Enzymatic cleavage of HS-GAGs by heparanase causes release of angiogenic growth factors leading to tumor cell migration. Heparanase is also over-expressed in tumors with significant correlation between metastatic potential and heparanase activity. Proteoglycans and their associated enzymes are thus significant drug targets of high biological relevance.
A functional consequence of strong PPC-HS binding has been shown in proof-of-concept studies confirming inhibition of the model pentasaccharide, Fondaparinux, …