title: Dual role of hydrophobic racemic thioesters of alpha-amino acids in the generation of isotactic peptides and co-peptides in water; implications for the origin of homochirality.
abstract: Thioesters of alpha-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(d(10))-Leu, first activated with N,N'-carbonyldiimidazole, then initiated with ethanethiol or with DL(d(3))-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 beta-sheets are formed and operate as stereoselective templates in the process of chain-elongation. Isotopic L:L(d(10))-Leu co-peptides were obtained in the polymerization of L(d(10))-Leu with L-LeuSEt. By contrast, mixtures of oligo-D-Leu and oligo-L(d(10))-Leu were obtained in the polymerization of mixtures of D-LeuSEt with activated L(d(10))-Leu. Isotactic co-peptides containing Leu and Val residues were formed in the polymerization of mixtures of activated DL(d(8))-Val with DL(d(3))-LeuSEt in water, implying that the racemic beta-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.
authors.affiliation: Department of Materials and Interfaces, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Roni A
authors.initials: RA
authors.lastname: Illos
authors.forename: Gilles
authors.initials: G
authors.lastname: Clodic
authors.forename: Gerard
authors.initials: G
authors.lastname: Bolbach
authors.forename: Isabelle
authors.initials: I
authors.lastname: Weissbuch
authors.forename: Meir
authors.initials: M
authors.lastname: Lahav
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D017433:Protein Structure, Secondary; D012996:Solutions; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D004952:Esters; D010455:Peptides; D012996:Solutions; D013438:Sulfhydryl Compounds; D014867:Water