Catalysis Driven by an Amyloid-Substrate Complex

Amyloid catalysis is an emerging area of research. Here, we report a new catalysis system, i.e., catalysis driven by amyloid-substrate complex (CASL), by exploiting amyloid binding with the ligands. The ammonium ion attached to the amyloid-binding motif was activated by its proximity to the amyloid catalyst, formed by Ac-Asn-Phe-Gly-Ala-Ile-Leu-NH2 (NL6) derived from islet amyloid polypeptide (IAPP), thereby promoting amine modifications in the acidic buffer. Consistent with the mode of action of CASL, the affinity of the substrates with amyloid catalysts correlated with the reaction yields. In addition, the direction of the amine extension from the amyloid-binding site markedly influenced the reaction progress. Crystallographic analysis and amide-to-ester substitution of the amyloid catalysts indicated that the carbonyl oxygen of the Phe–Gly amide bond of NL6 played a key role in activating the substrate amine via forming a hydrogen bond. With CASL, we succeeded in the selective conversion of substrates possessing equivalently reactive amine functionalities and introduced a new reaction scope (various amine modifications) to catalytic reactions using amyloids. The substrate-selective conversion ability of CASL significantly expands the applicability of catalytic amyloids in diverse research fields, including chemical biology and materials science.