Structural Screening of Short Peptide Amphiphiles with Autocatalytic Self‐Replication

Abstract There is great interest in developing small synthetic molecules that imitate some of the functions and behaviour of living beings. Here, we describe the structural screening of peptide amphiphiles with autocatalytic self‐replication, which mimics the perpetuation mechanisms of living matter. Our design uses two reactive precursors to generate self‐assembling peptide amphiphiles, which form micelles that catalyse their own synthesis. A collection of precursors with varying sizes was screened combinatorially, revealing a minimal tripeptide amphiphile required to trigger autocatalytic self‐replication. These results contribute to the structural simplification of synthetic supramolecular monomers with life‐like behaviour.