Ribonucleotides and RNA Promote Peptide Chain Growth

Abstract

All knownf orms of life use RNA-mediated polypeptide synthesis to produce the proteins encoded in their genes.B ecause the principal parts of the translational machinery consist of RNA, it is likely that peptide synthesis was achieved early in the prebiotic evolution of an RNA-dominated molecular world. How RNAa ttracted amino acids and then induced peptide formation in the absence of enzymes has been unclear.H erein, we show that covalent capture of an amino acid as ap hosphoramidate favors peptide formation. Peptide coupling is ar obust process that occurs with different condensation agents.K inetics showt hat covalent capture can accelerate chain growth over oligomerization of the free amino acid by at least one order of magnitude,sothat there is no need for enzymatic catalysis for peptide synthesis to begin. Peptide chain growth was also observed on phosphate-terminated RNAs trands.P eptide coupling promoted by ribonucleotides or ribonucleotide residues may have been an important transitional form of peptide synthesis that set in when amino acids were first captured by RNA.

Integrated synthesis of nucleotide and nucleosides influenced by amino acids

“…Recently, a mixture of amino acids and ribonucleotides in the presence of an activating agent (i.e. carbodiimide, ethylimidazole, or magnesium chloride) has been shown to lead to the formation of mixed polymers of nucleotides and amino acids 20,21,22 in addition to the formation of oligo-dipeptide backbones using thioester derivatives as mediators 23 .…”

How Small Heterocycles Make a Reaction Network of Amino Acids and Nucleotides Efficient in Water

“…Thec ondensation buffer drives genetic copying,denovo formation of RNAstrands, [22] and the formation of peptido-RNAs with peptides that are Nterminally linked to (oligo)ribonucleotides. [23] Peptide growth is faster than the background oligomerization of amino acids, [23] and the reaction system is robust, producing biochemically relevant molecules with all 20 proteinogenic amino acids. [24] Among the enzyme-free experimental systems known to us,t he condensation-buffer system produces the largest number of classes of biomolecules.Atypical assay will run continuously for days or weeks without human intervention, making it aprime candidate for studying the principles of an enzyme-free reaction network.…”

“…Either EDC-AMP or EI-AMP can react with nucleophiles, including the amino group of Gly,the 5'-phosphate of another nucleotide,o rar ibose diol, producing ap hosphoramidate (Gly-A), ap yrophosphate (AppA), or ap hosphodiester (AA), respectively.A ctivation of the carboxylate of free Gly or ribonucleotide-bound glycine (Gly-A), followed by nucleophilic attack of another amino acid, then leads to chain growth. Background reactions producing guanidines or Nacylureas are also considered, as well as an organocatalytic pathway to EDC hydrolysis via EI-EDC.A mino-acid oligo- merization in the absence of ribonucleotides was previously shown to be minimal, [23] and was therefore not included in the quantitative model. Likewise,further growth in the phosphodiester channel, back reactions,and other low-level reactions were not included in the quantitative treatment to keep the number of variables manageable.…”

Cooperative Ligation Breaks Sequence Symmetry and Stabilizes Early Molecular Replication

“…Any sequence space of even moderate length of for example 25 bases is so large (4 25 ≈ 10 15 ) that even with a significant volume and concentration, the sampling can only be sparse, meaning that each molecule would have a different sequence. It must be expected that even if such a very short sequence would have encoded and conferred an advantageous function for molecular evolution, it would not have had an impact on such a random pool of sequences.…”

“…The first information molecules did not have many mechanisms at their disposal. After the synthesis and accumulation of the first nucleotides, random sequences [15][16][17][18][19] could polymerize. Once they were long enough to bind at the given temperature, three-molecule complexes form, and one sequence would bind to two complementary sequences which can then be connected by a suitable chemical reaction.…”