Racemic β sheets in biochirogenesis

The transition from prebiotic racemic chemistry towards homochiral biology represents one of the unsolved riddles about the origin of life. 2] Its elucidation requires the development of possible scenarios for the conversion of racemic monomers into long bio-like homochiral (isotactic) polymers. 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. 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. 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, or enantiomorphous pleated b sheets, as suggested by Brack and Spach, 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 (256). Although it has been demonstrated that both these architectures might exert asymmetric induction in the polymerization reactions of activated a-amino acids, 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 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 oligo-