Peptide Self‐Replication Via Template‐Directed Ligation

Abstract A 32‐residue α‐helical peptide with a sequence similiar to that of the GCN4 leucine zipper region is shown to catalyze its own formation by accelerating the amide bond formation of a 17‐residue peptide, preactivated as a thiobenzyl ester, and a 15‐residue peptide with a N ‐terminal cysteine. The self‐replication process displays parabolic growth characteristics as revealed by a detailed kinetic analysis. Control reactions with single‐mutant peptides strongly support a mechanism in which a ternary and/or quaternary complex of the product with both peptide fragments act(s) as the catalytically active intermediate(s). Furthermore, these experiments reveal a remarkable sequence selectivity, as evidenced by the loss of autocatalytic activity as a result of a single replacement of leucine or valine residues with an alanine at the recognition interface.