Homochiral oligopeptides via surface recognition and enantiomeric cross impediment in the polymerization of racemic phenylalanine N‐carboxyanhydride crystals suspended in water

Abstract

As part of our program on the search of possible prebiotic routes for the formation of oligopeptides of homochiral sequence (isotactic) from racemic precursors in aqueous environment, we report the polymerization of racemic crystals of phenylalanine N-carboxyanhydrides, enantioselectively tagged with five deuterium atoms, suspended in water containing various amine initiators. Racemic mixtures of isotactic oligopeptides, comprising up to 25 repeat units of the same handedness, as the dominant component for each length, were observed in a MALDI-TOF mass spectrometry analysis. The racemic mixtures of the peptides could be desymmetrized by initiating the polymerization reaction with water-soluble methyl esters of either enantiopure alpha-amino acids or dipeptides. A three-step mechanism is proposed to account for these results: (i) Surface recognition of the chiral initiator by the chiral sites present at specific faces of the crystal; (ii) Oligopeptide elongation at the polymer/crystal interface; and (iii) Self-assembly of the short isotactic peptides into racemic antiparallel beta-sheets as templates followed by cross-enantiomeric impediment in the growth of enantiomeric chains at the peptide beta-sheet/crystal interface.