Development of Dipeptide‐Based Liquid Droplets and Fibrils as Enzyme‐Mimics

Coacervates are liquid droplets formed by liquid-liquid phase separation (LLPS) and are often considered as model protocells. The physicochemical environment inside coacervates has a unique microenvironment that can accelerate the chemical reactions. However, coacervates are generally made of multiple macromolecular components, and designing short peptide analogues capable of self-coacervation has proven difficult. Here a simple dipeptide for phase separation, made of one hydrophobic residue attached with polar histidine residue is presented. This dipeptide can self-coacervate into micrometre-sized liquid droplets. These droplets can act as microreactor for the hydrophobic reactants. This work delineates a minimalistic peptide that can self-assemble to coacervate resembling protocell. The designer peptide also shows fibrillar assembly at relatively low concentration at different pHs. The fibrillar morphologies with appended histidine residues make them an efficient catalyst as esterase mimic. Overall, this study provides a unique strategy for minimalistic design for supramolecular catalysts with applications in enzymology and synthetic biology.