Fig. 5.

Schematic model of the three modes of heparanase inhibition displayed by PG545 and its three analogues. Competitive inhibitors, such as compound 2, straddle the entire substrate binding region and completely occlude the catalytic site (panel A). Partial competitive inhibitors which are not large enough to bridge the two HS binding patches, such as compound 3, allow substrate access to the catalytic site (panel B). Parabolic competitive inhibitors, such as PG545 and compound 1, bind two molecules, the second molecule binding with higher affinity (panel C).