title: Homochiral oligopeptides generated by induced "mirror symmetry breaking" lattice-controlled polymerizations in racemic crystals of phenylalanine N-carboxyanhydride.
abstract: The formation of diastereoisomeric libraries of oligopeptides through the heterogeneous polymerization of racemic crystals of phenylalanine N-carboxyanhydride (PheNCA) is reported. The diastereoisomeric compositions of the oligopeptides formed on polymerization of (R,S) crystals incorporating the deuterium-tagged S enantiomer were determined by MALDI-TOF mass spectrometry. The racemic mixtures of the oligopeptides longer than pentamers are represented primarily by diastereoisomers of homochiral sequence and with peptides containing only one heterochiral repeating unit. A mechanism comprising the following three sequential steps to account for this unusual observation is proposed: 1) formation of dimers and trimers at a partially damaged liquid/solid interface, 2) chain propagation that takes place within the bulk of the crystal through a lattice-controlled "zipper-like" mechanism between homochiral molecules arranged in a head-to-tail motif to yield crystalline antiparallel beta-sheets of alternating oligopeptide chains of homochiral sequence of opposite handedness, and 3) enantiomeric cross-inhibition that results in chain termination. Induced desymmetrization of the racemic mixtures of the formed peptides was achieved by the polymerization of the mixed quasi-racemic crystals of (R)-PheNCA, ((S)-PheNCA), and (S)-ThieNCA (3-(2-thienyl)-alanine N-carboxyanhydride) of various compositions. These experiments resulted in the formation of nonracemic libraries of oligopeptides composed of homochiral chains of (R)-Phe and copolymers of randomly distributed (S)-Phe and (S)-Thie sequences. From these findings, we propose a stochastic model for the generation of libraries of nonracemic mixtures of oligopeptides from the polymerization of host (R,S)-PheNCA with racemic mixtures of other guest NCA amino acids dissolved in limited quantities in the crystal.
authors.affiliation: Department of Materials and Interfaces, Weizmann Institute of Science, 76100-Rehovot, Israel.
authors.forename: Jose Geraldo
authors.initials: JG
authors.lastname: Nery
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: D003460:Crystallization; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010649:Phenylalanine / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
chemical_list: D009842:Oligopeptides; D010649:Phenylalanine