Racemic β-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 oligo- peptides was determined by MALDI- TOF mass spectrometry, and the se- quences 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 deute- rium atoms. The process comprises sev- eral steps: 1) a Markov mechanism of asymmetric induction in the early stages of the polymerization yields li- braries of racemic oligopeptides en- riched with isotactic diastereoisomers, together with oligopeptide sequences containing enantiomeric blocks of ho- mochiral residues; 2) the short peptides self-assemble into racemic colloidal ar- chitectures that serve as regio-enantio- selective templates in the ensuing pro- cess of chain elongation; 3) homochiral residues of the amino acids located at the periphery of these colloidal aggre- gates exert efficient enantioselection, which results in the formation of long isotactic oligopeptides. The final diaste- reoisomeric distribution of the peptides depends upon the composition of the templates, which is determined by the concentration of the initiator. The race- mic mixtures of isotactic peptides can be desymmetrized by using enantio- pure methyl esters of a-amino acids as initiators.