α-Chymotrypsin catalyzed oligomerization of the "dipeptide lego" KL-ethyl ester (OEt) in aqueous media triggers a rapid sol-gel transition due to formation of alternating (KL)x. Resulting mixed chain oligomers, at alkaline pH, self-assemble into β-sheets. Thereafter, intermolecular backbone hydrogen bonding between peptides causes formation of physically entangled nanofibrillar networks.

A unique route to perfectly alternating oligopeptides is described. First, AG-OEt was prepared by standard chemical coupling. Then, AG-OEt was converted by papain-catalysis in 30 s to (AG)(x) (80%-yield, x = 9.4 ± 0.3). Extension of this strategy to other alternating peptide compositions as well as the importance of selecting a protease and reaction conditions that avoid competing transamidation and hydrolysis reactions is discussed.