Synthesis and evaluation of resins bearing substrate-like inhibitor functions for capturing copper amine oxidases

Abstract

The aim of this work was to make new tools available for investigating the interactions between enzymes and substrate-like inhibitors in copper amine oxidases (CAOs), a class of enzymes that controls important cellular processes, such as the crosslinking of elastin and collagen, cell proliferation and the regulation of intracellular polyamines. Starting from previous work, we synthesized the poly(N,N-dimethylacrylamide)-based resin R2 and the new TentaGel resins T3 and T4 obtained by ether bonding CAO substrate-like inhibitor moieties onto commercial TentaGel S-Br, which contains bromomethyl groups susceptible to nucleophilic substitution reactions. We used polyacrylamide gel electrophoresis (PAGE) experiments to determine the capability of the prepared resins to capture plasma amine oxidase (PAO) and diamine oxidase (DAO), members of the CAO family. The poly(N,N-dimethylacrylamide)-based resin R2 was able to block PAO and DAO, being the first insoluble polymeric material capable of capturing enzymes of the CAO family.