Peptide bond formation in gas‐phase ion/molecule reactions of amino acids: a novel proposal for the synthesis of prebiotic oligopeptides

Wincel, H.; Fokkens, R.H.; Nibbering, N. M. M.

doi:10.1002/(sici)1097-0231(20000215)14:3<135::aid-rcm851>3.3.co;2-d

Cited by 17 publications

(30 citation statements)

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“…The formation of amide bonds in the gas phase has been studied through computational work involving ion/molecule reactions (8) and has been demonstrated previously through uncatalyzed (9) and catalyzed reactions (10), photoexcitation reactions of proton-bound dimers (11,12), ion/molecule reactions (13)(14)(15), and directed ion/ion reactions (16)(17)(18) using Nhydroxysulfosuccinimide (sulfoNHS) esters. Gas phase separation of isomeric species has also been achieved through ion mobility techniques (19), which could be used as a further purification method.…”

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confidence: 97%

Efficient and directed peptide bond formation in the gas phase via ion/ion reactions

McGee

McLuckey

2014

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

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Amide linkages are among the most important chemical bonds in living systems, constituting the connections between amino acids in peptides and proteins. We demonstrate the controlled formation of amide bonds between amino acids or peptides in the gas phase using ion/ion reactions in a mass spectrometer. Individual amino acids or peptides can be prepared as reagents by (i) incorporating gas phaselabile protecting groups to silence otherwise reactive functional groups, such as the N terminus; (ii) converting the carboxyl groups to the active ester of N-hydroxysuccinimide; and (iii) incorporating a charge site. Protonation renders basic sites (nucleophiles) unreactive toward the N-hydroxysuccinimide ester reagents, resulting in sites with the greatest gas phase basicities being, in large part, unreactive. The N-terminal amines of most naturally occurring amino acids have lower gas phase basicities than the side chains of the basic amino acids (i.e., those of histidine, lysine, or arginine). Therefore, reagents may be directed to the N terminus of an existing "anchor" peptide to form an amide bond by protonating the anchor peptide's basic residues, while leaving the N-terminal amine unprotonated and therefore reactive. Reaction efficiencies of greater than 30% have been observed. We propose this method as a step toward the controlled synthesis of peptides in the gas phase.peptide ligation | ion chemistry T he formation of amide bonds between amino acids holds widespread interest as it is relevant to the origin of life. Although the process by which these early peptides were formed remains an open question, laboratory-based approaches for peptide synthesis have been in place for over a century. The first controlled synthesis of diglycine via hydrolysis of diketopiperazine by Fisher in 1901 (1) marked the beginning of a long path of development of peptide synthesis approaches. Since that time, peptide synthesis has undergone several developments, beginning as solution phase reactions and eventually evolving in 1963 with Merrifield's introduction of solid resins in peptide synthesis (2), more commonly referred to as solid phase peptide synthesis (SPPS). Although this technique has undergone a dynamic maturation over the past few decades, it is still regarded as expensive and inelegant (3, 4). Furthermore, there are still several challenges that are not likely to be overcome without a significant change to the synthesis approach, beyond inherent challenges such as, for example, solubility of reagents. SPPS requires significant use of protecting and deprotecting agents, cleaving agents, and other solvents for washing, drying, and dissolving the newly formed peptides. This method quickly becomes a rather wasteful approach when considering the sacrifices made to produce just a single amide bond (3). Alternative synthesis approaches, such as chemical ligation (5, 6) and molecular machine-mediated peptide synthesis (7), offer more elegant approaches despite maintaining several of the previously mentioned requirements.Amide b...

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confidence: 97%

Efficient and directed peptide bond formation in the gas phase via ion/ion reactions

McGee

McLuckey

2014

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

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“…Wincel and co-workers showed experimentally that gaseous ion/molecule reactions between amino acids promote the synthesis of protonated dipeptides. These dipeptides could then be chemically extended, suggesting the possibility of peptide bond formation in space [67].…”

Section: Models For Prebiotic Peptide Bond Formationmentioning

confidence: 99%

Peptide synthesis through evolution

Tamura

Alexander

2004

Cellular and Molecular Life Sciences (CMLS)

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Ribosome-catalyzed peptide bond formation is a crucial function of all organisms. The ribosome is a ribonucleoprotein particle, with both RNA and protein components necessary for the various steps leading to protein biosynthesis. Evolutionary theory predicts an early environment devoid of complex biomolecules, and prebiotic peptide synthesis would have started in a simple way. A fundamental question regarding peptide synthesis is how the current ribosome-catalyzed reaction evolved from a primitive system. Here we look at both prebiotic and modern mechanisms of peptide bond formation and discuss recent experiments that aim to connect these activities. In particular, RNA can facilitate peptide bond formation by providing a template for activated amino acids to react and can catalyze a variety of functions that would have been necessary in a pre-protein world. Therefore, RNA may have facilitated the emergence of the current protein world from an RNA or even prebiotic world.

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“…Peptide bond formation is a subject of intensive investigation by experiment, theory, and simulation. For example, the formation of peptide bonds in the gas phase was experimentally performed by various research groups . Clearly, the quantum mechanical calculations are useful to understand this mechanism with respect to structurally simple yet representative systems.…”

Section: Introductionmentioning

confidence: 99%

Uncatalyzed peptide bond formation between two double amino acid molecules in the gas phase

Czapla

Freza

2017

Int J Quantum Chem

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The gas phase mechanism for peptide bond formation between two double amino acid (DAA) molecules ((NH2)2C(COOH)2) is investigated in the absence of any catalysts. Two different paths, concerted and stepwise, each leading to both cis and trans DAA‐DAA dipeptide products (four mechanisms total) are examined on the basis of theoretical calculations carried out at the CCSD(T)/aug‐cc‐pVDZ//MP2/aug‐cc‐pVDZ level. The investigation indicates that the concerted mechanism leading to the trans configuration of the peptide bond in the DAA‐DAA dipeptide product is thermodynamically favored by about 5 kcal mol−1 and requires slightly less energy than the remaining pathways considered. Moreover, the peptide bond formation process between two DAA molecules in the gas phase resembles the analogous reactions between two natural amino acids.

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Peptide bond formation in gas‐phase ion/molecule reactions of amino acids: a novel proposal for the synthesis of prebiotic oligopeptides

Cited by 17 publications

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Efficient and directed peptide bond formation in the gas phase via ion/ion reactions

Efficient and directed peptide bond formation in the gas phase via ion/ion reactions

Peptide synthesis through evolution

Uncatalyzed peptide bond formation between two double amino acid molecules in the gas phase

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