Synthesis of Novel Glycolipid Mimetics of Heparan Sulfate and Their Application in Colorectal Cancer Treatment in a Mouse Model.

ABSTRACT: Heparan sulfate (HS) is a highly sulfated natural carbohydrate that plays crucial roles in cancer, inflammation, and angiogenesis. Heparanase (HPSE) is the sole HS degrading endoglycosidase that cleaves HS at structure-dependent sites along the polysaccharide chain. Overexpression of HPSE by cancer cells correlates with increased tumor size and enhanced metastasis. Previously we have shown that a tetramer HS mimetic is a potent HPSE inhibitor displaying remarkable anticancer activity in vivo. Building on that work, we report the synthesis and testing of a novel library of single entity trimer glycolipid mimetics that effectively inhibit HPSE at low nanomolar concentrations. A lipophilic arm was introduced to assess whether an improvement of pharmacokinetics and plasma residence time would

SUBMITTER: Spijkers-Shaw S 

PROVIDER: S-EPMC9324168 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature