Modulating Heparanase Activity: Tuning Sulfation Pattern and Glycosidic Linkage of Oligosaccharides.

ABSTRACT: Heparanase cleaves polymeric heparan sulfate (HS) molecules into smaller oligosaccharides, allowing for release of angiogenic growth factors promoting tumor development and autoreactive immune cells to reach the insulin-producing β cells. Interaction of heparanase with HS chains is regulated by specific substrate sulfation sequences. We have synthesized 11 trisaccharides that are highly tunable in structure and sulfation pattern, allowing us to determine how heparanase recognizes HS substrate and selects a favorable cleavage site. Our study shows that (1) N-SO₃^- at +1 subsite and 6-O-SO₃^- at -2 subsite of trisaccharides are critical for heparanase recognition, (2) addition of 2-O-SO₃^- at the -1 subsite a

SUBMITTER: Zhu S 

PROVIDER: S-EPMC7376576 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature