Racemic beta-sheets as templates for the generation of homochiral (isotactic) peptides from aqueous solutions of (RS)-valine or -leucine N-carboxy- anhydrides: relevance to biochirogenesis.

As part of our program on biochirogenesis of homochiral peptides from racemic precursors, we report the feasibility of obtaining peptides with homochiral sequences composed of up to 25 residues of the same handedness in the polymerization of racemic valine or leucine N-carboxyanhydrides in aqueous solutions, as initiated by amines. The composition of the oligopeptides was determined by MALDI-TOF mass spectrometry, and the sequences of some of the heterochiral diastereoisomers were studied by MALDI-TOF MS/MS performed on samples in which the S enantiomers of the monomer were tagged with deuterium atoms. The process comprises several steps: 1) a Markov mechanism of asymmetric induction in the early stages of the polymerization yields libraries of racemic oligopeptides enriched with isotactic diastereoisomers, together with oligopeptide sequences containing enantiomeric blocks of homochiral residues; 2) the short peptides self-assemble into racemic colloidal architectures that serve as regio-enantioselective templates in the ensuing process of chain elongation; 3) homochiral residues of the amino acids located at the periphery of these colloidal aggregates exert efficient enantioselection, which results in the formation of long isotactic oligopeptides. The final diastereoisomeric distribution of the peptides depends upon the composition of the templates, which is determined by the concentration of the initiator. The racemic mixtures of isotactic peptides can be desymmetrized by using enantiopure methyl esters of alpha-amino acids as initiators.

Homochiral oligopeptides generated via an asymmetric induction in racemic 2D crystallites at the air-water interface; the system ethyl/thio-ethyl esters of long-chain amphiphilic alpha-amino acids.

N(epsilon)-stearoyl-lysine-ethyl-ester (C18-OE-Lys) operates as an efficient desymmetrizing agent for the generation of homochiral oligopeptides via a reaction catalyzed by silver ions in two-dimensional (2D) quasi-racemic crystallites of the corresponding thio-ester (C18-TE-Lys) self-assembled on water.