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Figure 4.
A chemically modified, non-anticoagulant heparin is a potent inhibitor of heparanase enzymatic activity and melanoma lung colonization. Structure (top) and favored 3D conformation (bottom) of heparanase inhibitor 2 (HI-2) = heparin that is glycol-split (denoted by red circle) and N-acetylated (denoted by the blue circle). The enhanced flexibility of glycol-split heparin facilitates tight binding to heparanase (Hepa, bottom, left), resulting in potent inhibition of the enzyme activity and melanoma lung colonization (bottom, right).