N, N′-carbonyldiimidazole-induced diketopiperazine formation in aqueous solution in the presence of adenosine-5′-monophosphate

Brack, Andrè; Ehler, Kenneth W.; Orgel, Leslie E.

doi:10.1007/bf01739255

Cited by 22 publications

(8 citation statements)

References 6 publications

(4 reference statements)

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“…The presence of the dipeptide was confirmed by HPLC-ESI-MS (positive mode [M + H] = 373.2) as well as that of higher oligomers H-[Tyr(Me)] n -OH (with n = 3 to 5, [M + H] = 550.2, 727.3, 904.4 for peaks at r.t. 1.76 min, 1.93 min, 2.06 min, respectively, method C). By contrast reduced amounts of diketopiperazine cyclo -Tyr(Me)-Tyr(Me) formed confirming that the starting material lifetime was not sufficient for it to behave as a polymerization initiator leading to a dipeptide mixed anhydride prone to cyclization 27 . Under these conditions involving the presence of HCO 3 − , the polymerization into peptides thus proceeds through the NCA rather than directly from the starting material.…”

Section: Resultsmentioning

confidence: 99%

Evolutionary Importance of the Intramolecular Pathways of Hydrolysis of Phosphate Ester Mixed Anhydrides with Amino Acids and Peptides

Liu

Beaufils

Rossi

et al. 2014

Sci Rep

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Aminoacyl adenylates (aa-AMPs) constitute essential intermediates of protein biosynthesis. Their polymerization in aqueous solution has often been claimed as a potential route to abiotic peptides in spite of a highly efficient CO2-promoted pathway of hydrolysis. Here we investigate the efficiency and relevance of this frequently overlooked pathway from model amino acid phosphate mixed anhydrides including aa-AMPs. Its predominance was demonstrated at CO2 concentrations matching that of physiological fluids or that of the present-day ocean, making a direct polymerization pathway unlikely. By contrast, the occurrence of the CO2-promoted pathway was observed to increase the efficiency of peptide bond formation owing to the high reactivity of the N-carboxyanhydride (NCA) intermediate. Even considering CO2 concentrations in early Earth liquid environments equivalent to present levels, mixed anhydrides would have polymerized predominantly through NCAs. The issue of a potential involvement of NCAs as biochemical metabolites could even be raised. The formation of peptide–phosphate mixed anhydrides from 5(4H)-oxazolones (transiently formed through prebiotically relevant peptide activation pathways) was also observed as well as the occurrence of the reverse cyclization process in the reactions of these mixed anhydrides. These processes constitute the core of a reaction network that could potentially have evolved towards the emergence of translation.

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Section: Resultsmentioning

confidence: 99%

Evolutionary Importance of the Intramolecular Pathways of Hydrolysis of Phosphate Ester Mixed Anhydrides with Amino Acids and Peptides

Liu

Beaufils

Rossi

et al. 2014

Sci Rep

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“…1 D ) (5–9, 39). Formation of peptide oligomers or polymers is hindered by cyclization of dipeptides into DKP side products (11, 12, 40–43). The resolution is as follows: Facile ring opening of cyclic hydroxy acid dimers (dilactones, i.e., lactide and glycolide) and cyclic amino acid−hydroxy acid heterodimers (morpholinediones) promotes oligomerization.…”

Section: Discussionmentioning

confidence: 99%

Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions

Frenkel-Pinter

Haynes

Martin

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

106

105

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Numerous long-standing questions in origins-of-life research center on the history of biopolymers. For example, how and why did nature select the polypeptide backbone and proteinaceous side chains? Depsipeptides, containing both ester and amide linkages, have been proposed as ancestors of polypeptides. In this paper, we investigate cationic depsipeptides that form under mild dry-down reactions. We compare the oligomerization of various cationic amino acids, including the cationic proteinaceous amino acids (lysine, Lys; arginine, Arg; and histidine, His), along with nonproteinaceous analogs of Lys harboring fewer methylene groups in their side chains. These analogs, which have been discussed as potential prebiotic alternatives to Lys, are ornithine, 2,4-diaminobutyric acid, and 2,3-diaminopropionic acid (Orn, Dab, and Dpr). We observe that the proteinaceous amino acids condense more extensively than these nonproteinaceous amino acids. Orn and Dab readily cyclize into lactams, while Dab and Dpr condense less efficiently. Furthermore, the proteinaceous amino acids exhibit more selective oligomerization through their α-amines relative to their side-chain groups. This selectivity results in predominantly linear depsipeptides in which the amino acids are α-amine−linked, analogous to today’s proteins. These results suggest a chemical basis for the selection of Lys, Arg, and His over other cationic amino acids for incorporation into proto-proteins on the early Earth. Given that electrostatics are key elements of protein−RNA and protein−DNA interactions in extant life, we hypothesize that cationic side chains incorporated into proto-peptides, as reported in this study, served in a variety of functions with ancestral nucleic acid polymers in the early stages of life.

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“…However, the molecules have not been paid attention " To whom correspondence should be addressed. 20: 249-257, 1990.in a study of chemical evolution, but their formation has been considered to be an obstacle for the peptide chain elongation beyond dipeptide (Brack et aL, 1976;Orgel, 1978, 1979a). We have found that the reactions of DKP with amino acids or peptides in aqueous solution resulted in the formation and chain elongation of oligopeptides.…”

Section: Introductionmentioning

confidence: 97%

Diketopiperazine-mediated peptide formation in aqueous solution

Nagayama

Takaoka

Inomata

et al. 1990

Origins Life Evol Biosphere

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Though diketopiperazines (DKP) are formed in most experiments concerning the prebiotic peptide formation, the molecules have not been paid attention in the studies of chemical evolution. We have found that triglycine, tetraglycine or pentaglycine are formed in aqueous solution of glycine anhydride (DKP) and glycine, diglycine or triglycine, respectively. A reaction of alanine with DKP resulted in the formation of glycylglycylalanine under the same conditions. These results indicate that the formation of the peptide bonds proceeds through the nucleophilic attack of an amino group of the amino acids or the oligoglycines on the DKP accompanied by the ring-opening. The formation of glycine anhydride, di-, tri- and tetraglycine was also observed in a mixed aqueous solution of urea and glycine in an open system to allow the evaporation of ammonia. A probable pathway is proposed for prebiotic peptide formation through diketopiperazine on the primitive Earth.

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N, N′-carbonyldiimidazole-induced diketopiperazine formation in aqueous solution in the presence of adenosine-5′-monophosphate

Abstract: 3'(2')-O-glycyl-adenosine-5'-monophosphate is an intermediate in the conversion of N-[imidazoly-(1)-carbonyl]-glycine to diketopiperazine in the presence of adenosine-5'-monophosphate. The significance of these observations to prebiotic chemistry is discussed.

Cited by 22 publications

References 6 publications

Evolutionary Importance of the Intramolecular Pathways of Hydrolysis of Phosphate Ester Mixed Anhydrides with Amino Acids and Peptides

Evolutionary Importance of the Intramolecular Pathways of Hydrolysis of Phosphate Ester Mixed Anhydrides with Amino Acids and Peptides

Selective incorporation of proteinaceous over nonproteinaceous cationic amino acids in model prebiotic oligomerization reactions

Diketopiperazine-mediated peptide formation in aqueous solution

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