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

Abstract

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.

“Absolute” Asymmetric Polymerization within Crystalline Architectures: Relevance to the Origin of Homochirality

“…The mechanism of the solid-state polymerization of racemic α-amino acid-NCA crystals suggested that β-sheet templates might emerge also during the polymerization of such monomers dissolved in aqueous solutions, provided that the isotactic di-to tetra-peptides, which are formed stochastically in solution, can self-assemble into the more stable ap racemic β-sheets [77,78]. The structure of the β-sheets in the solution polymerization and chain-elongation processes will not be imposed by the monomer crystal, but will rather be dictated by the structures of the growing sites located at the rims.…”

Asymmetric amplification in amino acidsublimation involving racemic compound to conglomerate conversion

“…D,L-valine) in aqueous solution leads to peptides of homochiral sequences, a process of potential prebiotic interest. 24 …”

Life's Single Chirality: Origin of Symmetry Breaking in Biomolecules

“…Very recently, it was even shown that supramolecular aggregation on surfaces could result in drastic symmetry breaking and asymmetric amplification [62]. Lahav and coworkers have, for example, very recently and elegantly shown that homochiral oligopeptides can show spontaneous enantioenrichment during their formation reaction, due to the additional unexpected formation of racemic beta-sheets [19]. A further example is the theoretical recycling reaction model of Plasson et al [30], which is actually a model for polymerization with epimerization and has been studied in depth by Brandenburg et al [63].…”

“…Another possibility involves enantioenrichment in biopolymers through polymerization reactions (without overall asymmetric amplification) [19]. While it appears possible that polymerization itself led to the selection of homochiral strands of peptides or DNA -fed on a pool of racemic monomeric precursor molecules, it is unlikely that this could have occurred only at a single unique spot and only at a unique moment in time.…”