Oligopeptides and Copeptides of Homochiral Sequence, via beta-Sheets, from Mixtures of Racemic alfa-Amino Acids, in a One-Pot Reaction in Water; Relevance to Biochirogenesis

RONI A. ILLOS; FABRICIO R. BISOGNO; GILLES CLODIC; GERARD BOLBACH; ISABELLE WEISSBUCH; MEIR LAHAV

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

AMER CHEMICAL SOC

Año: 2008 vol. 130 p. 8651 - 8659

0002-7863

As part of our studies on the biochirogenesis of peptides of homochiral sequence during early evolution, the formation of oligopeptides composed of 14-24 residues of the same handedness in the polymerization of DL-leucine (Leu), DL-phenylalanine (Phe), and DL-valine (Val) in aqueous solutions, by activation with N,NŒ-carbonyldiimidazole and then initiation with a primary amine, in a one-pot reaction, was demonstrated by MALDI-TOF MS using deuterium enantio-labeled alpha-amino acids. The formation of long isotactic peptides is rationalized by the following steps occurring in tandem: (i) creation of a library of short diasteroisomeric oligopeptides containing isotactic peptides in excess in comparison to a binomial kinetics, as a result of an asymmetric induction exerted by the N-terminal residue of a given handedness; (ii) precipitation of the less soluble racemic isotactic penta- and hexapeptides in the form of beta-sheets that are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- long isotactic peptides is rationalized by the following steps occurring in tandem: (i) creation of a library of short diasteroisomeric oligopeptides containing isotactic peptides in excess in comparison to a binomial kinetics, as a result of an asymmetric induction exerted by the N-terminal residue of a given handedness; (ii) precipitation of the less soluble racemic isotactic penta- and hexapeptides in the form of beta-sheets that are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- was demonstrated by MALDI-TOF MS using deuterium enantio-labeled alpha-amino acids. The formation of long isotactic peptides is rationalized by the following steps occurring in tandem: (i) creation of a library of short diasteroisomeric oligopeptides containing isotactic peptides in excess in comparison to a binomial kinetics, as a result of an asymmetric induction exerted by the N-terminal residue of a given handedness; (ii) precipitation of the less soluble racemic isotactic penta- and hexapeptides in the form of beta-sheets that are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- long isotactic peptides is rationalized by the following steps occurring in tandem: (i) creation of a library of short diasteroisomeric oligopeptides containing isotactic peptides in excess in comparison to a binomial kinetics, as a result of an asymmetric induction exerted by the N-terminal residue of a given handedness; (ii) precipitation of the less soluble racemic isotactic penta- and hexapeptides in the form of beta-sheets that are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- activation with N,NŒ-carbonyldiimidazole and then initiation with a primary amine, in a one-pot reaction, was demonstrated by MALDI-TOF MS using deuterium enantio-labeled alpha-amino acids. The formation of long isotactic peptides is rationalized by the following steps occurring in tandem: (i) creation of a library of short diasteroisomeric oligopeptides containing isotactic peptides in excess in comparison to a binomial kinetics, as a result of an asymmetric induction exerted by the N-terminal residue of a given handedness; (ii) precipitation of the less soluble racemic isotactic penta- and hexapeptides in the form of beta-sheets that are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- long isotactic peptides is rationalized by the following steps occurring in tandem: (i) creation of a library of short diasteroisomeric oligopeptides containing isotactic peptides in excess in comparison to a binomial kinetics, as a result of an asymmetric induction exerted by the N-terminal residue of a given handedness; (ii) precipitation of the less soluble racemic isotactic penta- and hexapeptides in the form of beta-sheets that are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- was demonstrated by MALDI-TOF MS using deuterium enantio-labeled alpha-amino acids. The formation of long isotactic peptides is rationalized by the following steps occurring in tandem: (i) creation of a library of short diasteroisomeric oligopeptides containing isotactic peptides in excess in comparison to a binomial kinetics, as a result of an asymmetric induction exerted by the N-terminal residue of a given handedness; (ii) precipitation of the less soluble racemic isotactic penta- and hexapeptides in the form of beta-sheets that are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- long isotactic peptides is rationalized by the following steps occurring in tandem: (i) creation of a library of short diasteroisomeric oligopeptides containing isotactic peptides in excess in comparison to a binomial kinetics, as a result of an asymmetric induction exerted by the N-terminal residue of a given handedness; (ii) precipitation of the less soluble racemic isotactic penta- and hexapeptides in the form of beta-sheets that are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- polymerization of DL-leucine (Leu), DL-phenylalanine (Phe), and DL-valine (Val) in aqueous solutions, by activation with N,NŒ-carbonyldiimidazole and then initiation with a primary amine, in a one-pot reaction, was demonstrated by MALDI-TOF MS using deuterium enantio-labeled alpha-amino acids. The formation of long isotactic peptides is rationalized by the following steps occurring in tandem: (i) creation of a library of short diasteroisomeric oligopeptides containing isotactic peptides in excess in comparison to a binomial kinetics, as a result of an asymmetric induction exerted by the N-terminal residue of a given handedness; (ii) precipitation of the less soluble racemic isotactic penta- and hexapeptides in the form of beta-sheets that are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- long isotactic peptides is rationalized by the following steps occurring in tandem: (i) creation of a library of short diasteroisomeric oligopeptides containing isotactic peptides in excess in comparison to a binomial kinetics, as a result of an asymmetric induction exerted by the N-terminal residue of a given handedness; (ii) precipitation of the less soluble racemic isotactic penta- and hexapeptides in the form of beta-sheets that are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with L-1N-Mehistidine yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- yielded mixtures of copeptides containing both residues. In contrast, in the polymerization of the corresponding mixtures of L- + D-alpha-amino acids, the long oligopeptides were composed mainly from oligo- are delineated by homochiral rims; (iii) regio-enantiospecific chain elongation occurring heterogeneously at the beta-sheets/solution interface. Polymerization of L-Leu with L-isoleucine (Ile) or L-Phe with