Dual Role of Hydrophobic Racemic Thioesters of α-Amino Acids in the Generation of Isotactic Peptides and Co-peptides in Water; Implications for the Origin of Homochirality

Thioesters of α-amino acids are considered as plausible monomers for the generation of the primeval peptides. DL-Leucine-thioethyl esters (LeuSEt), where the L-enantiomer was tagged with deuterium atoms, undergo polycondensation in water or in bicarbonate or imidazole buffer solutions to yield mainly heterochiral (atactic) peptides and diketopiperazine, as analyzed by MALDI-TOF and ESI mass-spectrometry. In variance, when polymerization of DL(d₁₀)-Leu, first activated with N,N′-carbonyldiimidazole, then initiated with ethanethiol or with DL(d₃)-LeuSEt yielded a library of peptides up to 30 detectable residues where those of homochiral sequence (isotactic) are the dominant diastereoisomers. At these conditions, racemic β-sheets are formed and operate as stereoselective templates in the process of chain-elongation. Isotopic L:L(d₁₀)-Leu co-peptides were obtained in the polymerization of L(d₁₀)-Leu with L-LeuSEt. By contrast, mixtures of oligo-D-Leu and oligo-L(d₁₀)-Leu were obtained in the polymerization of mixtures of D-LeuSEt with activated L(d₁₀)-Leu. Isotactic co-peptides containing Leu and Val residues were formed in the polymerization of mixtures of activated DL(d₈)-Val with DL(d₃)-LeuSEt in water, implying that the racemic β-sheets exert regio-enantio-selection but not chemo-selection. A reaction pathway is suggested, where LeuSEt operates both as initiator of the reaction as well as a multimer.