Could Hydrophobicity of Sulfated Pseudo-Trisaccharides Derived from Repurposing Aminoglycoside Tobramycin Modulate the Enzymatic Activity of Heparanase?

ABSTRACT: Heparanase (HPSE) remodeling of the extracellular matrix makes it a crucial therapeutic target. The development of effective glycan-based HPSE inhibitors has been limited by bleeding and thromboembolic disorders. In this report, we present a structure-based design approach that rapidly generates a library of potent and selective HS mimetics, synthesized in 8 to 9 steps from readily available aminoglycoside tobramycin. Computational analyses indicate that hydrophobic molecular markers modulate HPSE activity. Consequently, we identified naphthalene-based N-sulfated tobramycin derivatives to enhance both stability and potency. These findings suggest that, in addition to the influence of charged groups, hydrophobic moieties substantially contribute to interactions with the heparin-bindi

SUBMITTER: Hotor M 

PROVIDER: S-EPMC12276975 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature