Prebiotic Peptides

The simplest amino acid, glycine, is almost always the one formed in highest yield in prebiotic syntheses. Thus, the first polycondensation experiments were carried out with glycine. Akabori (1955) and Hanabusa and Akabori (1959) reacted aminoace-tonitrile with kaolin at 403 108 K. The starting material is readily formed as follows  

After hydrolysis of the nitrile to the aminocarboxylic acid, the authors obtained the dipeptide diglycine (Gly-Gly) and the tripeptide Gly-Gly-Gly. 

Further studies were carried out mainly with glycine, since here the group R is simply hydrogen, so that no side reactions take place. In addition, glycine does not have an asymmetric carbon atom, so that chirality problems cannot occur (see Sect. 9.4). Steinman and Cole (1967) used dicyandiamide as a condensa-tion/dehydration agent a dipeptide was formed in about 1.2% yield. 

As already described in Sect. 5.3, the activation of the amino acid can occur at the acid functionality  

Using condensation agents such as dicyandiamide or its dimer 

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If prebiotic peptides and/or proteins were in fact initially formed in aqueous solution (the hypothesis of biogenesis in the primeval ocean ), the energy problems referred to above would have needed to be solved in order for peptide synthesis to occur. As discussed in Sect. 5.3, there is some initial experimental evidence indicating that the formation of peptide bonds in aqueous media is possible. An important criterion for the evolutionary development of biomolecules is their stability in the aqueous phase. The half-life of a peptide bond in pure water at room temperature is about seven years. The stability of the peptide bond towards cleavage by aggressive compounds was studied by Synge (1945). The following relative hydrolysis rates were determined experimentally, with the relative rate of hydrolysis for the dipeptide Gly-Gly set equal to unity ... 

Luke, B. T., A. G. Gupta, G. H. Loew, J. G. Lawless, and D. H. White. 1984. Theoretical Investigation of the Role of Clay Edges in Prebiotic Peptide Bond Formation. I. Structures of Acetic Acid, Glycine, H2S04, H3P04, Si(OH)4, and Al(OH)4. Int. I. Quantum Chem. Quantum Biol. Symp. 11, 117-135. 

Bujdak, J., Slosiarikova, H., Texler, N., Schwendinger, M., and Rode, B. M. (1994). On the possible role of montmorillonites in prebiotic peptide formation. Monats. Chem., 125, 1033-9. 

Suwannachot, Y. and Rode, B. M. (1999). Mutual amino acid catalysis in salt-induced peptide formation supports this mechanism s role in prebiotic peptide evolution. Origin Life Evol. Biosph., 5,463-71. 

From the point of view of prebiotic chemistry, it can be concluded from the thermodynamic and kinetic stability of amides that the formation of prebiotic peptides has very probably required catalysts and/or dehydrating or activating agents. But their spontaneous formation could not be com-... 

J. Rabinowitz and A. Hampai (1984). Quantitative polyphosphate-induced prebiotic peptide formation in H20 by addition of certain azoles and ions. J. Mol. Evol., 21, 199-201. 

Bujdak, J., H. Slosiarikova, N. Texler, M. Schwendinger, and B. M. Rode. 1994. On the possible role of montmorillonite in prebiotic peptide formation. Monatshefte fur Chemie 125 1033-1039. 

The self-condensation of glycine to triglycine at pH 6.7-8.9 is increased 10-20 fold in the presence of catalysts of which 1,2,4-triazole is one of the best. The reaction is not noted in basic solutions but the effect is maximal at the pH thought to be that of primitive oceans. The linking of triazole with prebiotic peptide syntheses is speculative and far fetched but not irrational (81C59). 

Many processes have been proposed for the formation of prebiotic peptides. Peptide bond formation from free amino acids can become thermodynamically favorable using physical or chemical means for dehydration (6, 36). Alternatively, activated amino acid derivatives are capable of polymerizing into oligopeptides in aqueous solution. A pathway for the formation of a-amino acid thioesters starting from sugar precursors has been discussed (37). a-Amino acid A-carboxyanhydrides (NCAs) correspond to... 

Taillades J, BeuzeUn I, Garrel L, Tabacik V, Bled C, Commeyras A. A -carbamoyl-a-amino acids rather than free a-amino acids formation in the primitive hydrosphere a novel proposal for the emergence of prebiotic peptides. Orig. Life Evol. Biosph. 1998 28 61-77. 

Now back to the different routes of prebiotic peptide synthesis. 

The differences in enantioselectivity, often used for the classification of hydantoinases based on their biotechnological value, therefore do not reflect the evolutionary relationship of the different hydantoinases, which are forming a more diverse group of enzymes than was assumed earlier (for more details see reviews references1141 and1131). This protein superfamily probably has its origin in the prebiotic conditions of the primitive earth, where N-carbamoyl-a-amino acids rather than free a-amino acids are supposed to be the first synthons for prebiotic peptides in the evolution today1151. 

Paecht-Horowitz, M., 1974. The possible role of clays in prebiotic peptide synthesis. Origins Life 5 173—187. 

Prebiotic peptides, peptides formed before the origin of life. Most likely, amino acids were already present on primitive Earth. They are supposed to have been produced in the primitive atmosphere, in hydrothermal vents, or to have been imported in meterorites. a-Amino acids can undergo peptide formation by activation with carbon monoxide under hot aqueous conditions in the presence of freshly co-precipitated colloidal (Fe,Ni)S. Peptides may have been formed via —>-N-carboxy anhydrides. A replicative synthesis involving aminoacyl-RNA intermediates has also been suggested. The question of whether a peptide/protein world preceded the RNA-driven template synthesis, or whether RNA and proteins should not be viewed as eti-ologically discrete entities in the origin of life, is still under debate [V. Borsenberger et al., Chem. Biodivers. 2004, 1, 203 C. Huber et al., Science 2003, 301, 938 A. Brack, Chem. Biodivers. 2007, 4, 665]. 

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