Enzymes are highly efficient and selective macromolecular catalysts. The three-dimensional structure of the polypeptide scaffolds supramolecularly bind substrartes and creates an optimal local environment to facilitate the catalysis. Synthetic polymers have been explored to serve similar roles as proteins to enhance the performance of traditional small molecule catalysts. Single-chain nanoparticles (SCNPs) receive considerable attention for their controllable chemical and folding structures. A group of copper containing SCNPs have been developed to perform copper(I)-mediated alkyne–azide cycloaddition (CuAAC), “click” reactions. The nanoparticles are shown to have significantly higher activity and selectivity when compared to analogous small molecule catalysts, especially under biological related conditions. Structure-activity relationships and reaction mechanisms are studied, showing the polymeric scaffolds bind substrates in an enzyme-like manner. The catalysts perform highly efficient catalysis on both small molecules and proteins, but operate in two modes: an “uptake mode” where small molecule substrates bind inside the polymer pockets and an “attach mode” that involves surface binding of protein substrates. The versatility of the structures and functions of the nanoparticles lead to applications in protein surface modification, protein binder finding, drug synthesis and screening. More broadly, the results show that synthetic polymer scaffolds hold huge potentials for developing artificial metalloenzymes, especially for biological related applications.

Single-chain nanoparticle-based clickase

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.