Improvement of N-benzoylation catalysis driven by an amyloid–substrate complex

Abstract

Nucleophilic reactions of amines are important chemical transformations, but the reactions are incompatible with acidic buffer conditions. Azo-stilbene is a motif that binds to amyloids formed by accumulation of β-sheet peptides. We previously reported that the amino group attached to azo-stilbene is activated by proximity to an amyloid catalyst, promoting nucleophilic reactions in acidic buffers. Here, we show that we could improve the N-benzoylation yield for what was previously a difficult substrate by (1) derivatizing an amyloid catalyst, (2) modulating the amyloid morphology with His, and (3) adding thioflavin-T as a reaction additive. These results are predicted to accelerate the application of the amine modification catalysis system driven by the amyloid–substrate complex and to advance research on functional molecules containing an azo-stilbene motif.