Peptide Formation Reaction Research Articles

The Role of the CuCl Active Complex in the Stereoselectivity of the Salt-Induced Peptide Formation Reaction: Insights from Density Functional Theory Calculations.

The salt-induced peptide formation (SIPF) reaction is a prebiotically plausible mechanism for the spontaneous polymerization of amino acids into peptides on early Earth. Experimental investigations of the SIPF reaction have found that in certain conditions, the l enantiomer is more reactive than the d enantiomer, indicating its potential role in the rise of biohomochirality. Previous work hypothesized that the distortion of the CuCl active complex toward a tetrahedral-like structure increases the central chirality on the Cu ion, which amplifies the inherent parity-violating energy differences between l- and d-amino acid enantiomers, leading to stereoselectivity. Computational evaluations of this theory have been limited to the protonated-neutral l + l forms of the CuCl active complex. Here, density functional theory methods were used to compare the energies and geometries of the homochiral (l + l and d + d) and heterochiral (l + d) CuCl-amino acid complexes for both the positive-neutral and neutral-neutral forms for alanine, valine, and proline. Significant energy differences were not observed between different chiral active complexes (i.e., d + d, l + l vs. l + d), and the distortions of active complexes between stereoselective systems and non-selective systems were not consistent, indicating that the geometry of the active complex is not the primary driver of the observed stereoselectivity of the SIPF reaction.

Protocell self-assembly driven by sodium trimetaphosphate.

The co-evolution of peptide formation and membrane self-assembly is considered an essential step in the origin of life. In this study, we systematically investigated the sodium trimetaphosphate (P3m)-activated peptide formation reaction of Phe in an alkaline decanoic acid-decanol vesicle system. The experimental results showed that the peptide formation could competitively occur with N-acyl amino acid (NAA) formation. NAA formation did not follow the traditional P3m-activated peptide formation reaction involving the intermediate cyclic acylphosphoramidate (CAPA), but a phosphoric acid- decanoic acid mixed anhydride intermediate. NAA can form vesicles independently and reduce the critical vesicle concentration of the fatty-acid vesicles. 11 other representative amino acids, namely Ala, Asp, Glu, Gly, Ile, Leu, Pro, Ser, Thr, Val, and Arg, were selected for investigation. All of them reacted with decanoic acid to form NAA via the activation effect of P3m. Our experimental results indicate that the P3m activation effect can provide diversified raw membrane materials to form and stabilize protocell membranes; moreover, the small peptides, such as Phe-Leu, formed in the same reaction system can induce the amplification of primitive cells. This implies that synergistic symbiosis between membrane and peptide can be realized via the P3m activation effect.

On the Origin of Sequence.

Three aspects which make planet Earth special, and which must be taken in consideration with respect to the emergence of peptides, are the mineralogical composition, the Moon which is in the same size class, and the triple environment consisting of ocean, atmosphere, and continent. GlyGly is a remarkable peptide because it stimulates peptide bond formation in the Salt-Induced Peptide Formation reaction. The role glycine and aspartic acid play in the active site of RNA polymerase is remarkable too. GlyGly might have been the original product of coded peptide synthesis because of its importance in stimulating the production of oligopeptides with a high aspartic acid content, which protected small RNA molecules by binding Mg2+ ions. The feedback loop, which is closed by having RNA molecules producing GlyGly, is proposed as the essential element fundamental to life. Having this system running, longer sequences could evolve, gradually solving the problem of error catastrophe. The basic structure of the standard genetic code (8 fourfold degenerate codon boxes and 8 split codon boxes) is an example of the way information concerning the emergence of life is frozen in the biological constitution of organisms: the structure of the code contains historical information.

Peptide formation mechanism on montmorillonite under thermal conditions.

The oligomerization of amino acids is an essential process in the chemical evolution of proteins, which are precursors to life on Earth. Although some researchers have observed peptide formation on clay mineral surfaces, the mechanism of peptide bond formation on the clay mineral surface has not been clarified. In this study, the thermal behavior of glycine (Gly) adsorbed on montmorillonite was observed during heating experiments conducted at 150°C for 336h under dry, wet, and dry-wet conditions to clarify the mechanism. Approximately 13.9% of the Gly monomers became peptides on montmorillonite under dry conditions, with diketopiperazine (cyclic dimer) being the main product. On the other hand, peptides were not synthesized in the absence of montmorillonite. Results of IR analysis showed that the Gly monomer was mainly adsorbed via hydrogen bonding between the positively charged amino groups and negatively charged surface sites (i.e., Lewis base sites) on the montmorillonite surface, indicating that the Lewis base site acts as a catalyst for peptide formation. In contrast, peptides were not detected on montmorillonite heated under wet conditions, since excess water shifted the equilibrium towards hydrolysis of the peptides. The presence of water is likely to control thermodynamic peptide production, and clay minerals, especially those with electrophilic defect sites, seem to act as a kinetic catalyst for the peptide formation reaction.

Effects of metal ions and pH on the formation and decomposition rates of di- and tri-peptides in aqueous solution

The recent discovery of active deep-sea hydrothermal systems venting high-pH fluids suggests that the prebiotic chemistry of the hydrothermal systems of early Earth may have been more diverse than previously thought. To determine the most favorable conditions for prebiotic oligomerization, the effects of metal ions (Ca2+, Mg2+, Zn2+, Fe2+, Mn2+, and Cu2+) and pH on the formation and decomposition rates of glycylglycine (GlyGly), glycylglycylglycine (GlyGlyGly), and diketopiperazine (DKP) in aqueous solution were investigated. Glycine (Gly) solutions containing metal ions were heated for 1–74 days at 140°C under various pH conditions and the samples were analyzed by high-performance liquid chromatography. GlyGly and DKP were produced in all samples regardless of the presence or absence of metal ions. GlyGly yields were higher under basic conditions (pH 9.8–9.9) than under acidic or neutral conditions. Moreover, GlyGly yields in the presence of Cu2+ and Zn2+ were higher than in the absence of Cu2+ and Zn2+; in the presence of metal ions other than Cu2+ and Zn2+, GlyGly yields were lower. The dimerization rate constant of Gly (k1) increased in the presence of Cu2+. GlyGlyGly was only produced in samples with Cu2+ and the yield was 5 times higher under basic conditions (pH 9.8) than under acidic (pH 3.4) or neutral (pH 7.1) conditions. However, other metal ions inhibited prebiotic peptide synthesis by catalyzing hydrolysis or chelation with amino acids. These results reflect the high stability of Cu2+ complexes with amino acids or peptides in the salt-induced peptide formation reaction, particularly at high pH. Although elongation of oligopeptides was not favored, formation of metal–amino acid or metal–short peptide chelates may have facilitated primitive biological functions and expanded prebiotic reaction fields because of their mobility in the Earth’s early oceans.

Potassium Ions are More Effective than Sodium Ions in Salt Induced Peptide Formation

Prebiotic peptide formation under aqueous conditions in the presence of metal ions is one of the plausible triggers of the emergence of life. The salt-induced peptide formation reaction has been suggested as being prebiotically relevant and was examined for the formation of peptides in NaCl solutions. In previous work we have argued that the first protocell could have emerged in KCl solution. Using HPLC-MS/MS analysis, we found that K+ is more than an order of magnitude more effective in the L-glutamic acid oligomerization with 1,1'-carbonyldiimidazole in aqueous solutions than the same concentration of Na+, which is consistent with the diffusion theory calculations. We anticipate that prebiotic peptides could have formed with K+ as the driving force, not Na+, as commonly believed.

Isoleucine as a possible bridge between exogenous delivery and terrestrial enhancement of homochirality

We report a highly enantioselective oligomerization of isoleucine stereomers in the salt-induced peptide formation reaction under plausibly prebiotic earth conditions. Up to 6.5-fold superiority in reactivity of L-isoleucine was observed, compared to its D-enantiomer, after 14 evaporation cycles in the presence of Cu(2+) and NaCl. Since isoleucine is among the proteinogenic amino acids that were found enantioenriched in meteorites, this present work may further correlate the extraterrestrial delivery and endogenous production of biological homochirality by virtue of a protein constituent rather than the rarely occurring α-methylated amino acids.

Arginine in the salt-induced peptide formation reaction: enantioselectivity facilitated by glycine, l- and d-histidine

The salt-induced peptide formation reaction has been proposed as a conceivable preliminary to the prebiotic evolution of peptides. In the present paper, the behaviour of arginine is reported for this reaction together with a discussion of the catalytic effects of glycine, and L- and D-histidine. Importantly, the behaviour of the two histidine enantiomers is different. Both histidine enantiomers perform better than glycine in enhancing the yields of arginine dipeptide with L-histidine being more effective than D-histidine. Yields in the presence of histidine are up to 70 times greater than for arginine solutions alone. This compares with 4.2 times higher in the presence of glycine. This difference is most pronounced in the most concentrated (containing 80 mM arginine) reaction solution where arginine has the lowest reactivity. A distinct preference for dimerisation of L-arginine also appears in the 80 mM cases for catalyses of other amino acids. This phenomenon is different from the behaviour of aliphatic amino acids, which display obvious inherent enantioselectivity for the L-stereomers in the SIPF reaction on their own rather than when catalysed by glycine or histidine.

Towards peptide formation inside the channels of a new divinylaniline-bridged periodic mesoporous organosilica

The first synthesis of a new highly ordered divinylaniline-bridged periodic mesoporous organosilica (PMO) with crystal-like pore walls and further chemical modification of the amino groups on the inner surface of the product by a peptide formation reaction with a chiral amino acid are reported.

Catalytic effects of histidine enantiomers and glycine on the formation of dileucine and dimethionine in the salt-induced peptide formation reaction

The salt-induced peptide formation (SIPF) reaction takes place readily under mild reaction conditions and proceeds via a copper complex. Its ease of reaction and the universality for prebiotic scenarios add weights to the arguments in favour of the importance of peptide and proteins in the tug of war with the RNA world hypothesis. In addition, the SIPF reaction has a preference for L-form amino acids in dipeptide formation, casting light on the puzzle of biohomochirality, especially for the amino acids with aliphatic side chains. A detailed investigation on the behaviour of aliphatic leucine in the SIPF reaction is presented in this paper, including the catalytic effects of glycine, L- and D-histidine as well as the stereoselectivity under all the reaction conditions above. The results show a relatively low reactivity and stereoselectivity of leucine in the SIPF reaction, while both glycine and histidine enantiomers remarkably increase the yields of dileucine by factors up to 40. Moreover, a comparative study of the effectiveness of L- and D-histidine in catalysing the formation of dimethionine was also carried out and extends the scope of mutual catalysis by amino acid enantiomers in the SIPF reaction.

The catalytic effect of l- and d-histidine on alanine and lysine peptide formation

A starting phase of chemical evolution on our ancient Earth around 4billion years ago was the formation of amino acids and their combination to peptides and proteins. The salt-induced peptide formation (SIPF) reaction has been shown to be appropriate for this condensation reaction under moderate and plausible primitive Earth conditions, forming short peptides from amino acids in aqueous solution containing sodium chloride and Cu(II) ions. In this paper we report results about the formation of dialanine and dilysine from their monomers in this reaction. The catalytic influence of l- and d-histidine dramatically increases dialanine yields when starting from lower alanine concentrations, but also dilysine formation is markedly boosted by these catalysts. Attention is paid to measurable preferences for one enantiomeric form of alanine and lysine in the SIPF reaction. Alanine, especially, shows stereospecific behaviour, mostly in favour of the l-form.

Chemical evolution toward the origin of life

AbstractNumerous hypotheses about how life on earth could have started can be found in the literature. In this article, we give an overview about the most widespread ones and try to point out which of them might have occurred on the primordial earth with highest probability from a chemical point of view. The idea that a very early stage of life was the "RNA world" encounters crucial problems concerning the formation of its building blocks and their stability in a prebiotic environment. Instead, it seems much more likely that a "peptide world" originated first and that RNA and DNA took up their part at a much later stage. It is shown that amino acids and peptides can be easily formed in a realistic primordial scenario and that these biomolecules can start chemical evolution without the help of RNA. The origin of biohomochirality seems strongly related to the most probable formation of the first peptides via the salt-induced peptide formation (SIPF) reaction.

Possible Origins of Biohomochirality

The origin of biohomochirality and the reasons, why this form of homochirality (L-amino acids, D-sugars, etc.) and not the mirror image case was preferred have been the subject of numerous hypotheses, but a definitive solution to this riddle that might be strongly correlated with the origin of life itself has not been found to date. In this paper different pathways trying to explain the origin of biohomochirality are reviewed, inter alia the chance hypothesis, spontaneous resolution mechanisms, preferential adsorption on chiral surfaces, the interaction of interstellar organic dust clouds with circularly polarised light and subsequent transport to earth via meteorites, and a possible preference for one enantiomeric form due to parity violation in weak nuclear interactions. In the Salt-Induced Peptide Formation (SIPF) reaction a preference for the L-form of several amino acids was observed. The active complex in this reaction contains a central copper ion which, due to its high atomic number, provides larger parity violating energy differences (PVEDs). In combination with the geometry of this complex that features a central chirality at this copper ion and further chiral influence through chiral amino acid ligands a completely new aspect to explain biohomochirality is presented.

The Possible Influence ofL-Histidine on the Origin of the First Peptides on the Primordial Earth

One of the most unsettled problems of prebiotic evolution and the origin of life is the explanation why one enantiomeric form of biomolecules prevailed. In the experiments presented in this paper, the influence of L-histidine on the peptide formation in the Salt-Induced Peptide Formation (SIPF) reaction of the enantiomeric forms of valine, proline, serine, lysine, and tryptophan, and the catalytic effects in this first step toward the first building blocks of proteins on the primordial earth were investigated. In the majority of the produced dipeptides, a remarkable increase of yields was shown, and the preference of the L-amino acids in the peptide formation in most cases cannot be denied. In summary, our data provide further experimental evidence for the plausibility of the SIPF reaction and point at a possible important role of L-histidine in the chemical evolution on the primordial Earth.

Catalytically Increased Prebiotic Peptide Formation: Ditryptophan, Dilysine, and Diserine

"Mutual" amino acid catalysis of glycine on the formation of ditryptophan, dilysine, and diserine in the prebiotically relevant Salt-Induced Peptide Formation (SIPF) Reaction was investigated varying the starting concentration and chirality of the educt amino acid, and analyzing the increase of yield resulting from this catalytic effect. Our results show the possibility of an amplified diverse pool of peptides being available for chemical evolution of larger peptides and proteins using also these more complicated amino acids for the evolution of more complex functions in future biochemical cycles and thus for the emergence of life. Catalytic effects are especially high in the case of serine, the most basic amino acid of the three, but are also significant for the other two examples investigated in the present work. Besides that, especially for serine, but also in the case of tryptophan, differences in catalytic yield increase according to the chiral form of the amino acid used could be observed.

Catalytic effects of glycine on prebiotic divaline and diproline formation

The catalytic effects of the simple amino acid glycine on the formation of diproline and divaline in the prebiotically relevant salt-induced peptide formation (SIPF) reaction was investigated in systems of different amino acid starting concentrations and using the two enantiomeric forms of the respective amino acid. Results show an improved applicability of the SIPF reaction to prebiotic conditions, especially at low amino acid concentrations, as presumably present in a primordial scenario, and indicate excellent conditions and resources for chemical evolution of peptides and proteins on the early earth. For valine, furthermore differences in catalytic yield increase are found indicating a chiral selectivity of the active copper complex of the reaction and showing a connection to previously found enantiomeric differences in complex formation constants with amino acids.

Stereoselective differentiation in the Salt-induced Peptide Formation reaction and its relevance for the origin of life

All living organisms on earth are almost totally made up of biomolecules of only one chiral form. For example, proteins are built almost exclusively of l-amino acids, and sugars are composed of d-saccharides, a fact that is usually referred to as biohomochirality. Its origin is the center of numerous investigations and theories but is not really elucidated yet. The results of experimental investigations of peptide formation in a prebiotically relevant scenario, as described in this paper, give indications on a possible pathway for the synthesis of homochiral l-peptides in the course of the Salt-induced Peptide Formation (SIPF) reaction.

Indications towards a stereoselectivity of the salt-induced peptide formation reaction

Different reaction yields for l- and d-alanine in the salt-induced peptide formation (SIPF) reaction, differences in the circular dichroism spectra and the complex formation constants of the involved chlorocuprate complexes point at a stereoselective differentiation between the two stereoisomers in the SIPF reaction and give a possible explanation towards the origin of homochirality in the process of the origin of life. An explanation of the observed effects can for the time being only be based on assumptions but could possibly be related to the inherent chirality of the Cu II ion as a central atom of the [CuCl(gly)(glyH 2)(H 2O) 2] + complex due to parity violation in weak interactions and to amplification of chirality related to the structural properties of the complex.

Preferential amino acid sequences in alumina-catalyzed peptide bond formation

The catalytic effect of activated alumina on amino acid condensation was investigated. The readiness of amino acids to form peptide sequences was estimated on the basis of the yield of dipeptides and was found to decrease in the order glycine (Gly), alanine (Ala), leucine (Leu), valine (Val), proline (Pro). For example, ∼15% Gly was converted to the dipeptide (Gly 2), 5% to cyclic anhydride (cyc(Gly 2)) and small amounts of tri- (Gly 3) and tetrapeptide (Gly 4) were formed after 28 days. On the other hand, only trace amounts of Pro 2 were formed from proline under the same conditions. Preferential formation of certain sequences was observed in the mixed reaction systems containing two amino acids. For example, almost ten times more Gly-Val than Val-Gly was formed in the Gly+Val reaction system. The preferred sequences can be explained on the basis of an inductive effect that side groups have on the nucleophilicity and electrophilicity, respectively, of the amino and carboxyl groups. A comparison with published data of amino acid reactions in other reaction systems revealed that the main trends of preferential sequence formation were the same as those described for the salt-induced peptide formation (SIPF) reaction. The results of this work and other previously published papers show that alumina and related mineral surfaces might have played a crucial role in the prebiotic formation of the first peptides on the primitive earth.

Glycine and diglycine as possible catalytic factors in the prebiotic evolution of peptides.

Mutual catalytic effects within the Salt-Induced Peptide Formation (SIPF) Reaction might be one little puzzle piece in the complicated process of the formation of complex peptidic systems and their chemical evolution on the prebiotic earth. The catalytic effects of glycine and diglycine on the formation of dipeptides from mixed amino acid systems in the SIPF Reaction was investigated for systems with leucine, proline, valine and aspartic acid and showed to result in a significant increase of the yield of the majority of the produced dipeptides. The results of the experiments strongly confirm previous theories on the catalytic mechanism and show the ability of the SIPF Reaction to produce a very diverse set of peptide products with relevance to the formation of a biosphere.