Abstract:Alpha-N-Carbamoyl amino acid (CAA), whose conditions of formation in a prebiotic hydrosphere have been described previously (Taillades et al. 1998), could have been an important intermediate in prebiotic peptide synthesis through reaction with atmospheric NOx. Nitrosation of solid CAA (glycine or valine derivative) by a 4/1 NO/O2 gaseous mixture (1 atm) yields N-carboxyanhydride (NCA) quantitatively in less than 1 h at room temperature. The crude solid NCA undergoes quantitative oligomerization (from trimer to… Show more
“…N-Carbamoyl amino acids have been shown to be very interesting precursors of Ncarboxyanhydrides [52] [53]. N-Phosphoryl a-amino acids lead to oligopeptides via a five-membered cyclic pentacoordinate phosphoric-carboxylic mixed anhydrides resembling the N-carboxyanhydrides [54].…”
Amino acids were most likely available on the primitive Earth, produced in the primitive atmosphere or in hydrothermal vents. Import of extraterrestrial amino acids may have represented the major supply, as suggested by micrometeorite collections and simulation experiments in space and in the laboratory. Selective condensation of amino acids in water has been achieved via N-carboxy anydrides. Homochiral peptides with an alternating sequence of hydrophobic and hydrophilic amino acids adopt stereoselective and thermostable beta-pleated sheet structures. Some of the homochiral beta-sheets strongly accelerate the hydrolysis of oligoribonucleotides. The beta-sheet-forming peptides have also been shown to protect their amino acids from racemization. Even if peptides are not able to self-replicate, i.e., to replicate a complete sequence from the mixture of amino acids, the accumulation of chemically active peptides on the primitive Earth appears plausible via thermostable and stereoselective beta-sheets made of alternating sequences.
“…N-Carbamoyl amino acids have been shown to be very interesting precursors of Ncarboxyanhydrides [52] [53]. N-Phosphoryl a-amino acids lead to oligopeptides via a five-membered cyclic pentacoordinate phosphoric-carboxylic mixed anhydrides resembling the N-carboxyanhydrides [54].…”
Amino acids were most likely available on the primitive Earth, produced in the primitive atmosphere or in hydrothermal vents. Import of extraterrestrial amino acids may have represented the major supply, as suggested by micrometeorite collections and simulation experiments in space and in the laboratory. Selective condensation of amino acids in water has been achieved via N-carboxy anydrides. Homochiral peptides with an alternating sequence of hydrophobic and hydrophilic amino acids adopt stereoselective and thermostable beta-pleated sheet structures. Some of the homochiral beta-sheets strongly accelerate the hydrolysis of oligoribonucleotides. The beta-sheet-forming peptides have also been shown to protect their amino acids from racemization. Even if peptides are not able to self-replicate, i.e., to replicate a complete sequence from the mixture of amino acids, the accumulation of chemically active peptides on the primitive Earth appears plausible via thermostable and stereoselective beta-sheets made of alternating sequences.
“…Condensation of N-carboxy anhydrides (NCA), conversely, begins to be accepted as a prebiotic method of chain formation [10], and, in fact, the group of Commeyras has approached the very problem of the prebiotic formation of sequential peptides by this method [10 -12] (see also Blocher et al [13]). However, also in this case, the critical question of the production of multiple identical copies of long (30 or more) cooligopeptides could not yet be achieved.…”
We describe an experimental procedure to mimic the formation of long (over 40 residues) co-oligopetide sequences in many identical copies which may have occurred in the prebiotic molecular evolution. The basic hypothesis is that chain formation is based on the stepwise fragment condensation of randomly generated short oligopeptides, whereby the elongation takes place under the contingent environmental constraints (solubility, pH, salinity), which eliminate most of the products, and thus determine the selection towards one particular small set of chains. The present work aims at verifying the validity of this scheme. In order to do so, we utilize a classic synthetic procedure based on the Merrifield solid-phase synthesis of peptides for the synthesis of randomly produced peptides as well as for their stepwise fragment condensation. Thus, starting from a library of peptides with n=10, the first condensation step produces a library of 16 peptides with 20 residues each (n=20), of which only four remain water-soluble and, therefore, capable to undergo the next fragment condensation step. This gives rise to 16 peptides with n=30, out of which twelve precipitate out under the chosen pH and buffer conditions and are eliminated. Finally, a 44-residue-long water-soluble de novo protein is obtained. This has no homologies or similarities with extant proteins, and, based on circular dichroism (CD), it assumes a stable three-dimensional folding. In agreement with CD data, molecular-modelling simulations suggest an helical fold for the protein with poor, if any, structural homology with known proteins. The implication of this procedure as a general mechanism for the etiology of de novo macromolecular sequences and globular proteins in the origin of life is briefly discussed.
“…Synthesis: The synthesis of the first generation of polyA C H T U N G T R E N N U N G (llysine) was carried out by a three-step sequence (Scheme 2) by implementing the knowledge from our research group [17,28,29] and by starting from N-carbamoyl derivative CLysA C H T U N G T R E N N U N G (Tfa), which was prepared by a straightforward NcarbamA C H T U N G T R E N N U N G oylation of N e -trifluoroacetyl-l-lysine. [29] NO + O 2 -promoted nitrosation [28] of C-LysA C H T U N G T R E N N U N G (Tfa) in acetonitrile gave monomer LysA C H T U N G T R E N N U N G (Tfa)-NCA, which was then reacted in aqueous sodium hydrogen carbonate (pH 6.5) to give N e -protected oligoA C H T U N G T R E N N U N G (l-lysine) G1P.…”
Section: Resultsmentioning
confidence: 99%
“…[15] As an example based on peptide bonds, Klok et al [14,16] reported the synthesis of dendritic graft polyA C H T U N G T R E N N U N G (l-lysine)s by iterative co-polycondensation of two differently N e -protected amino acid N-carboxyanhydrides (NCA) in dimethylformamide, followed by the selective removal of one of these sets of protecting groups; a final, complete deprotection step then afforded the desired dendritic graft polyA C H T U N G T R E N N U N G (llysine). [14] Our recent investigations on NCA chemistry in water (in connection with their possible key role in the emergence of life through the prebiotic chemistry of peptides), [17][18][19] gave us the opportunity to address the synthesis of lysine arborescent polymer in an original manner. Because of their high Abstract in French: Nous dØcrivons la synthse et la caractØ-risation de nouvelles architectures arborescentes de polyA C H T U N G T R E N N U N G (llysine), nommØes dendrimres greffØs de lysine (DGL).…”
The synthesis and characterisation of new arborescent architectures of poly(L-lysine), called lysine dendrigraft (DGL) polymers, are described. DGL polymers were prepared through a multiple-generation scheme (up to generation 5) in a weakly acidic aqueous medium by polycondensing N(epsilon)-trifluoroacetyl-L-lysine-N-carboxyanhydride (Lys(Tfa)-NCA) onto the previous generation G(n-1) of DGL, which was used as a macroinitiator. The first generation employed spontaneous NCA polycondensation in water without a macroinitiator; this afforded low-molecular-weight, linear poly(L-lysine) G1 with a polymerisation degree of 8 and a polydispersity index of 1.2. The spontaneous precipitation of the growing N(epsilon)-Tfa-protected polymer (GnP) ensures moderate control of the molecular weight (with unimodal distribution) and easy work-up. The subsequent alkaline removal of Tfa protecting groups afforded generation Gn of DGL as a free form (with 35-60% overall yield from NCA precursor, depending on the DGL generation) that was either used directly in the synthesis of the next generation (G(n+1)) or collected for other uses. Unprotected forms of DGL G1-G5 were characterised by size-exclusion chromatography, capillary electrophoresis and (1)H NMR spectroscopy. The latter technique allowed us to assess the branching density of DGL, the degree of which (ca. 25%) turned out to be intermediate between previously described dendritic graft poly(L-lysines) and lysine dendrimers. An optimised monomer (NCA) versus macroinitiator (DGL G(n-1)) ratio allowed us to obtain unimodal molecular weight distributions with polydispersity indexes ranging from 1.3 to 1.5. Together with the possibility of reaching high molecular weights (with a polymerisation degree of ca. 1000 for G5) within a few synthetic steps, this synthetic route to DGL provides an easy, cost-efficient, multigram-scale access to dendritic polylysines with various potential applications in biology and in other domains.
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