Generation of Oligopeptides with Homochiral Sequences by Topochemical Reactions within Racemic Crystals of Phenylalanine‐<i>N</i>‐carboxyanhydride

Nery, José Geraldo; Bolbach, G.; Weissbuch, Isabelle; Lahav, Meir

doi:10.1002/anie.200351114

Cited by 44 publications

(23 citation statements)

References 27 publications

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“…One can see that the dipeptides obtained with both catalysts exhibit an almost random distribution, whereas, for the tri-to hexapeptides, homochiral sequences are overrepresented in all the experiments. This result is similar to that obtained in the absence of rac-DPG, which can be rationalized in terms of the packing arrangement of the rac-C 18 -TE-Lys crystallites [17] and a preferred reaction pathway between homochiral monomer [25] molecules along the a-axis (Fig. 4,a).…”

supporting

confidence: 87%

Amphiphilic Homochiral Oligopeptides Generated via Phase Separation of Nonracemic α‐Amino Acid Derivatives and Lattice‐Controlled Polycondensation in a Phospholipid Environment

Rubinstein

Bolbach

Weygand³

et al. 2003

Helvetica Chimica Acta

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Dedicated to Professor Duilio Arigoni on the occasion of his 75th birthday Racemic S-ethyl thioesters of N e -stearoyllysine ( S-ethyl (R,S)-2-amino-6-(stearoylamino)hexanethioate) and S-ethyl thioesters of g-stearyl glutamic acid ( stearyl (R,S)-4-amino-5-(ethylsulfanyl)-5-oxopentanoate) self-assemble as separated two-dimensional crystalline monolayers within an achiral phospholipid environment of racemic 1,2-dipalmitoylglycerol (DPG) and 1,2-dipalmitoylglycero-3-phosphoethanolamine (DPPE), as demonstrated by grazing-incidence X-ray-diffraction (GIXD) measurements performed on the surface of H 2 O. Lattice-controlled polycondensation within these crystallites with deuterium-enantiolabeled monomers was initiated by injecting aqueous solutions of Ag or I 2 /KI beneath the monolayers, which yielded mixtures of diastereoisomeric oligopeptides containing up to six to eight repeating units, as analyzed by MALDI-TOF mass spectrometry. Analysis of the diastereoisomeric distribution showed an enhanced relative abundance of the oligopeptides with homochiral sequences containing three or more repeating units. Within the DPPE monolayers, the nucleophilic amino group of the phospholipid operates as an initiator of polymerization at the periphery of the monomer two-dimensional crystallites. Enhanced relative abundance of enantiomerically enriched homochiral oligopeptides was obtained by the polycondensation of nonracemic monomers. This enhancement indicated a phase separation into racemic and enantiomorphous monomer crystallites within the phospholipid environment, although this separation could not be observed directly by GIXD. A possible role that might have been played by crystalline assemblies for the abiotic generation and amplification of oligopeptides with homochiral sequences is discussed.Introduction. ± One of the central enigmata in the abiotic origin of life is related to the question of how homochiral biopolymers have been formed under prebiotic conditions. An accepted scenario for early formation of biopolymers from abiotic atomic or molecular ingredients is based on the assumption that primitive polymers might have been formed on surfaces then concentrated and sequestered within primeval membrane-like films that were subsequently converted into proto-cells to form primitive vesicle-like architectures capable of engulfing the polymers for further self-replication [1 ± 3]. This scenario invokes an essential role played by early membrane-like materials in the form of primitive proto-cells. It does not, however, consider the formation of homochiral polymers from racemates or from nonracemic mixtures of activated racemic monomers of low enantiomeric imbalance within these membrane-like environments.

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confidence: 87%

Amphiphilic Homochiral Oligopeptides Generated via Phase Separation of Nonracemic α‐Amino Acid Derivatives and Lattice‐Controlled Polycondensation in a Phospholipid Environment

Rubinstein

Bolbach

Weygand³

et al. 2003

Helvetica Chimica Acta

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“…The kinetics of chain-elongation during the polymerization of NCA monomer crystals suspended in aqueous solutions of the amine initiator, in general, may differ substantially from the reactivity in hexane suspensions, 34,35 where only up to decapeptides were obtained at the same n-butylamine initiator concentration. The interaction of the amphiphilic initiator molecules with the hydrophobic and hydrophilic monomer crystal faces may differ in the two suspending liquids.…”

Section: Computation Proceduresmentioning

confidence: 99%

“…In the first pathway, the crystalline lattice may control the stereospecificity of the short oligopeptides, dipeptides to tetrapeptides, via a possible ''zipper like'' mechanism where the NH 2 group of the growing peptide approaches the C a À ÀO of a neighboring monomer molecule still in its original position in the crystal, as proposed previously. 34 The second pathway considers a diffusion of the monomer molecules toward the growing peptide chains. In such a process, the role of the crystal lattice is to control the diffusion pathway of the monomer molecules.…”

Section: Proposed Pathway Of the Reaction With Enantiopure Initiatormentioning

confidence: 99%

“…This scenario comprises the self-assembly of the chiral molecules into structured racemic self-assemblies, followed by lattice-controlled reaction between molecules of the same handedness that convert the reactant into racemic mixtures of isotactic polymers. These studies comprise polymerization of amphiphilic monomers self-assembled within two-dimensional crystallites at the air/water interface [27][28][29][30][31][32][33] and the polymerization of racemic phenylalanine N-carboxyanhydride (R,S) PheNCA (Scheme 1) crystals 34,35 suspended in hexane solutions. However, hexane is not a prebiotic solvent; therefore, it is of interest to perform this reaction in aqueous suspensions.…”

Section: Introductionmentioning

confidence: 99%

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Homochiral oligopeptides via surface recognition and enantiomeric cross impediment in the polymerization of racemic phenylalanine N‐carboxyanhydride crystals suspended in water

Nery

Eliash

Bolbach³

et al. 2007

Chirality

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As part of our program on the search of possible prebiotic routes for the formation of oligopeptides of homochiral sequence (isotactic) from racemic precursors in aqueous environment, we report the polymerization of racemic crystals of phenylalanine N-carboxyanhydrides, enantioselectively tagged with five deuterium atoms, suspended in water containing various amine initiators. Racemic mixtures of isotactic oligopeptides, comprising up to 25 repeat units of the same handedness, as the dominant component for each length, were observed in a MALDI-TOF mass spectrometry analysis. The racemic mixtures of the peptides could be desymmetrized by initiating the polymerization reaction with water-soluble methyl esters of either enantiopure alpha-amino acids or dipeptides. A three-step mechanism is proposed to account for these results: (i) Surface recognition of the chiral initiator by the chiral sites present at specific faces of the crystal; (ii) Oligopeptide elongation at the polymer/crystal interface; and (iii) Self-assembly of the short isotactic peptides into racemic antiparallel beta-sheets as templates followed by cross-enantiomeric impediment in the growth of enantiomeric chains at the peptide beta-sheet/crystal interface.

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“…This disadvantage might be overcome if the short polymers of homochiral sequence (isotactic) would self-assemble into ordered architectures that could exert steric control on the ensuing process of chain elongation occurring at the polymer/crystal interface. [15][16][17] The operation of such interplay requires an understanding of the role played by the structure of the monomer crystal at the early stages of the reaction, its role in dictating the self-assembly of the formed peptides into supramolecular architectures, such as a helices or b sheets, and the ultimate role played by the latter as stereospecific or enantioselective templates in the ensuing stages of polymer propagation. Here, we provide support for this hypothesis for the solidstate polymerisation of racemic crystals of valine N-carboxyanhydride (ValNCA, Scheme 1) and leucine N-carboxyanhydride (LeuNCA) suspended in hexane or water solutions of a primary-amine initiator.…”

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confidence: 99%

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

Eliash¹,

Nery²,

Rubinstein³

et al. 2007

Chemistry A European J

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As part of our program on the biochirogenesis of homochiral peptides, we report the formation of racemic parallel (p) beta sheets composed of alternating R and S chains of up to 14-15 repeat units of the same handedness through the polymerisation of (R,S)-valine N-carboxyanhydride (NCA) crystals suspended in aqueous solutions of a primary amine as the initiator. The occurrence of such a lattice-controlled reaction accompanied by a reduction in volume implies the operation of a mechanism that differs from that of the common solid-state polymerisation in vinyl systems. The topotacticity of the reaction is explained through the operation of a multistep nonlinear process comprising lattice control coupled with an asymmetric induction in the formation of homochiral short peptides followed by their self-assembly into racemic p beta sheets, which operate as efficient templates in the ensuing process of enantioselective chain elongation at the polymer/crystal interface. The composition of the diastereoisomeric libraries of oligopeptides was determined by MALDI-TOF and MALDI-TOF-TOF MS analyses of the products obtained from monomers enantioselectively labelled with deuterium. The structure of the p beta sheets could be determined by initiating the polymerisation reaction with water-soluble esters of enantiopure alpha-amino acids or short peptides. The same reaction performed with the monomer crystals suspended in hexane yielded a complex mixture of diastereoisomeric oligopeptides, thus highlighting the indispensable role played by water in controlling the stereoselectivity of the reaction. By contrast, polymerisation of (R,S)-leucine NCA crystals, with a different packing arrangement that presumably does not endorse the formation of periodic peptide templates, yielded, both in aqueous and hexane suspensions, libraries of peptides dominated by heterochiral diastereoisomers.

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Generation of Oligopeptides with Homochiral Sequences by Topochemical Reactions within Racemic Crystals of Phenylalanine‐N‐carboxyanhydride

Cited by 44 publications

References 27 publications

Amphiphilic Homochiral Oligopeptides Generated via Phase Separation of Nonracemic α‐Amino Acid Derivatives and Lattice‐Controlled Polycondensation in a Phospholipid Environment

Amphiphilic Homochiral Oligopeptides Generated via Phase Separation of Nonracemic α‐Amino Acid Derivatives and Lattice‐Controlled Polycondensation in a Phospholipid Environment

Homochiral oligopeptides via surface recognition and enantiomeric cross impediment in the polymerization of racemic phenylalanine N‐carboxyanhydride crystals suspended in water

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

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