Naturally occurring enzymes generally catalyze chemical reactions in a substrate-specific manner by forming a unique enzyme-substrate complex when both structures match (Fig. ). Thus, the catalytic activity of the enzyme is provided by the proximity effect mediated by tight binding of the substrate to the active site of the enzyme. Inspired by the mode of action of enzyme catalysis, we envisioned substrate-selective conversion using amyloids, leading to the concept of CASL (Fig. ). Specifically, we anticipated that a ligand molecule (regarded as a substrate) that potently binds to the cross-β-sheet structure of amyloids would be selectively activatable for chemical conversion due to the close proximity to the amyloid catalyst. To validate the CASL concept, we focused on amine modification in buffer media (Fig. ). Although amine modifications in organic solvents are classical transformations, reactions in aqueous buffers are not facile. Neutral to slightly acidic buffers, which should be useful conditions due to the mildness, protonate alkyl amines (pKa ≈ 10) to generate ammonium salts lacking nucleophilicity. The general base reagents are also protonated and inactive in terms of the deprotonation ability of the substrates under the same conditions. The enzyme, however, deprotonates the ammonium salt of the substrate to a free amine based on the tight binding between the two in buffer. Inspired by a mechanism in which the backbone amide functionality of the enzymes withdraws the protons of the substrates, we were motivated to introduce the reaction system to amine modifications in buffer using CASL. We began by examining N-benzoylation of an alkyl amine attached to azobenzene derivative (1), a well-known amyloidbinding motif (Fig. ). In the absence of amyloid, the amine was unsurprisingly inactive to the benzoyl (Bz) donor in acidic buffer (pH 6.0) at 37˚C (entry 1). We therefore used amyloid catalysts composed of penta-to-octapeptides. The N-terminal amines of the peptides were capped by acetylation to avoid interference with the target reaction. Also, the C-terminus of the peptides was amide-capped because the carboxylate functionality was thought to inhibit amyloid formation. The amyloid-forming propensity of the peptides was evaluated using a thioflavin-T (ThT) dye assay whose fluorescence intensity increases according to the extent of the cross-β-sheet layering. We express the logarithm value of the ThT intensity (API) as an index of the amyloidogenic potential. First, five kinds of short peptides known to form amyloids (API range: 6-9) were screened for their facilitating effects on N-benzoylation (entries 2-6). The amyloid formed by Ac-Asn-Phe-Gly-Ala-Phe-NH2 (derived from TDP-43 ) and Ac-Phe-Tyr-Leu-Leu-Tyr-Tyr-NH2 (derived from β2 microglobulin ) hardly promoted the benzoylation reaction at all (entries 2 and 3). Ac-Ala-Ile-Ile-Gly-Leu-Met-NH2 (derived from amyloid β ) and Ac-Asn-Phe-Gly-Ser-Val-Gln-Phe-Val-NH2 (derived from lactadherin ), however, moderately promoted N-benzoylation (entries 4 and 5, 32% and 52%), whereas Ac-Asn-Phe-Gly-Ala-Ile-Leu-NH2 (NL6) derived from islet amyloid polypeptide (IAPP) 18 remarkedly promoted the reaction (entry 6, 78%). The reaction rate was also faster for NL6 compared with the others (Fig. ). Under conditions in which the pH was made basic instead of adding an amyloid catalyst, conversion to the desired product 1-Bz was not achieved in high yield (Fig. ), indicating the superiority of CASL with NL6 for N-benzoylation in buffer.