J

-02C

Glu-225

FIGURE 10.8 A. Recognition sequence of heparan sulfate. B. Mechanism of the reaction catalyzed by heparanase.

with reduced molecular sizes, and one of these compounds, the phosphosulfo-mannan PI-88, is in clinical trials in several cancers.24 PI-88 is a mixture of chemically sulfated oligosaccharides, ranging from di- to hexasaccharides and with the majority (60%) being pentasaccharides. Besides being a heparanase inhibitor, PI-88 also inhibits angiogenesis by antagonizing the interactions of proangiogenic growth factors (e.g., VEGF and bFGF) and their receptors with HS.

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