Dynamic Combinatorial Optimization of In Vitro and In Vivo Heparin Antidotes.

ABSTRACT: Heparin-like macromolecules are widely used in clinics as anticoagulant, antiviral, and anticancer drugs. However, the search of heparin antidotes based on small synthetic molecules to control blood coagulation still remains a challenging task due to the physicochemical properties of this anionic polysaccharide. Here, we use a dynamic combinatorial chemistry approach to optimize heparin binders with submicromolar affinity. The recognition of heparin by the most amplified members of the dynamic library has been studied with different experimental (SPR, fluorescence, NMR) and theoretical approaches, rendering a detailed interaction model. The enzymatic assays with selected library members confirm the correlation between the dynamic covalent screening and the in vitro heparin inhibitio

SUBMITTER: Carbajo D 

PROVIDER: S-EPMC8958503 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature