Design and Synthesis of Nanostructured Peptoids Assemblies that Mimic Natural Carbonic Anhydrases

Abstract

Artificial Carbonic Anhydrase (CA) mimics that resemble natural CA have gained increasing attention recently due to their low-cost synthesis, high tunability, and high efficiency. However, it remains a significant challenge to precisely control nanostructure-based CA mimics and achieve high catalytic efficiency. Peptoids, poly-N-substituted glycines, offer unique advantages for this purpose because they can self-assemble into various nanostructures with high crystallinity and stability and serve as the template for precise control over the active sites that mimic CAs. By carefully designing the hydrophilic and hydrophobic regions of the peptoid and the terminal Zn-coordination site, the self-assembled peptoid materials showed excellent hydrolytic efficiency as CA mimics to hydrolyze p-nitrophenyl acetate (p-NPA), a model substrate for testing the esterase catalytic activity. Moreover, the peptoid CA mimics can be operated under basic conditions yielding higher activity. The importance of nanostructure to catalytic efficiency was also demonstrated by comparing numerous control studies. Finally, some other peptoids, which self-assemble into helices, rods, and sheets, are presented to have the potential for developing CA mimics in the future.