SUBSTANCES DIRECTED AGAINST SPECIFIC SEQUENCE ESSENTIAL FOR HEPARANASE CATALYTIC ACTIVITY END USES THEREOF AS HEPARANASE INHIBITORS

摘要

Abstract The present invention relates to amino acid sequences derived from the 50 kDa subunit of heparanase, particularly in the regions between amino acid residues Lys158-Asp171, Gln270 to Lys280 and Lys411 to Arg432 of human heparanase and any functional fragments thereof. Heparin-bindng domains are comprised within said amino acid sequences. The invention further provides compositions for the inhibition of heparanase glycosidase catalytic activity, comprising as active ingredient peptides comprising said amino acid sequences. The invention also provides an antibody directed to said sequences, in particular to the region between Lys158-Asp171, and compositions and uses thereof as heparanase inhibitors. The invention further relates to a screening method for specific heparanase inhibitors and provides compositions comprising said heparanase inhibitors and methods for the treatment of heparanase related disorders.