Racemic β Sheets in Biochirogenesis

Abstract

The transition from prebiotic racemic chemistry towards homochiral biology represents one of the unsolved riddles about the origin of life. [1,2] Its elucidation requires the development of possible scenarios for the conversion of racemic monomers into long bio-like homochiral (isotactic) polymers. [3][4][5] The polymerization of a-amino acids in buffer solutions has been reported to yield small amounts of isotactic oligopeptides, in a process that departs from the Bernoulli random kinetics; however, the mechanism responsible for this deviation was not elucidated. [6] A way to override the disadvantage of the tendency to form polymeric chains composed from heterochiral repeat units in the polymerization of racemic monomers may require the emergence of supramolecular architectures as intermediates in nonlinear processes. [7][8][9] A commonly accepted hypothesis for the formation of long primeval peptides of homochiral sequence from racemic precursors suggests the involvement of either a helices, as proposed by Wald, [10] or enantiomorphous pleated b sheets, as suggested by Brack and Spach, [11] as templates. Their formation requires, however, oligopeptides composed from eight (or more) repeat units of the same handedness in the polymerization of racemates, a process that obeys binomial kinetics with a probability of 1 molecule out of 2 8 (256). [12][13][14][15] Although it has been demonstrated that both these architectures might exert asymmetric induction in the polymerization reactions of activated a-amino acids, [16] their role in the formation of long homochiral peptides from racemates has not been supported by laboratory experiments.By contrast, we anticipate on kinetic grounds that racemic b sheets composed of mixtures of isotactic oligopeptides, delineated by chiral rims, might be advantageous architectures, provided that they can operate as templates for the formation of long peptides. The formation of these b sheets should be much faster as it depends upon the concentration of both the R and the S isotactic chains, whereas that of the enantiopure pleated b sheets depends upon the concentration of only one of the enantiomers. Although racemic antiparallel (ap) b sheets had been proposed by Pauling and Corey [17] to be closely similar to the natural pleated ap b sheets, they have been overlooked as possible participants in chemobiogenesis.Here we show that racemic ap b sheets play a dominant role in the generation of libraries of isotactic oligopeptides comprising up to 25 repeat units of the same handedness in the polymerization reaction of racemic N-carboxyanhydrides of valine (ValNCA) or leucine (LeuNCA) in aqueous solution and in the presence of primary amines (Scheme 1).(R,S)-ValNCA and (R,S)-LeuNCA, enantioselectively tagged with deuterium (98 %), were polymerized in water with n-butylamine (25 mol %, pH 6-7.5) and analyzed by MALDI-TOF MS. The diastereomeric compositions of oligoVal and oligo-Leu in the product samples are shown in Figure 1 a and b. In these spectra, the peaks for the isotactic oligo...

Self‐Replicating Amphiphilic β‐Sheet Peptides

“…[44,45] In addition, the origin of molecular chirality was also probed in peptide chain-elongation experiments, showing that significant homochiral amplification of peptides is obtained by the formation of b sheets. [46,47] Our results support these hypoth- N 1 (1), or E g and N g (1 gg )), at (22 AE 1) 8C in aqueous 3-(4-morpholinyl)-1-propanesulfonic acid (MOPS) buffer solutions at pH 7, and with tris(2-carboxyethyl)phosphine (TCEP; 5 mm) as a reducing agent (see the Experimental Section in the Supporting Information). The amounts of formed product were determined by HPLC using a foreign ABA-labeled peptide as standard (Supporting Information, Figure S3).…”

Homochiral Oligopeptides via a Lattice‐Controlled Polymerisation in Racemic Crystals of Valine N‐Carboxyanhydride Suspended in Aqueous Solutions

“…In this system, we cannot ignore the possibility that a small number of the isotactic peptides were formed in the aqueous solution due to some dissolution of the monomer. [4] …”

“…[17] If enantiomorphous pleated sheets are formed, those composed of isotactic oligopeptides of the same absolute configuration as the initiator will be formed in excess. [4] The MALDI-TOF mass spectra of the water-soluble and water-insoluble diastereoisomeric peptides generated in the polymerisation reaction of (R,S)-ValNCA crystals suspended in aqueous solutions containing the (S)-Val-OMe initiator are shown in Figure 6a and b. Oligopeptides comprising up to 14 repeat units were detected and we noticed that the water-soluble isotactic di-and tripeptides formed in excess are of the same absolute configuration as that of the initiator (Figure 6a). On the other hand, beyond the tetrapeptides (Figure 6b), there is a reversal in sign of the ee value of the isotactic oligopeptides and this ee value remains almost unchanged for the longer peptides, as shown in Figure 7a.…”

“…However, parallel studies of polymerisation in aqueous solutions to which the initiator was added five minutes after the complete monomer dissolution demonstrated the formation of racemic antiparallel (ap) b sheets. [4] According to the packing arrangement of the (R,S)-ValNCA monomer crystal, the racemic isotactic peptides should self-assemble into racemic p b sheets, although they are anticipated, on the basis of the results of polymerisation in aqueous solution, [4] to be energetically less stable than the ap b sheets. This self-assembly is illustrated in Figure 5, in which two parallel isotactic chains of opposite handedness can be accommodated in this architecture without introducing high strain along the a direction of the monomer lattice.…”

Evolução biomolecular homoquiral: a origem e a amplificação da quiralidade nas moléculas da vida

“…Lahav e colaboradores propuseram a possibilidade de gerar petídeos isotáticos e copeptídeos contendo até 25 resíduos de mesma quiralidade, a partir de α-aminoácidos ativados ou não racêmicos em diversos ambientes reacionais. 62 Em algumas reações, folhas-β racêmicas semelhantes a partículas coloidais emergem e operam como moldes estereosseletivos na formação de peptídeos homoquirais. Tais moldes deveriam apreciar uma considerável vantagem enantiosseletiva em um ambiente pré-biótico.…”