Ribonucleotides and RNA Promote Peptide Chain Growth

Abstract

All known forms of life use RNA-mediated polypeptide synthesis to produce the proteins encoded in their genes. Because 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 RNA attracted amino acids and then induced peptide formation in the absence of enzymes has been unclear. Herein, we show that covalent capture of an amino acid as a phosphoramidate favors peptide formation. Peptide coupling is a robust process that occurs with different condensation agents. Kinetics show that covalent capture can accelerate chain growth over oligomerization of the free amino acid by at least one order of magnitude, so that there is no need for enzymatic catalysis for peptide synthesis to begin. Peptide chain growth was also observed on phosphate-terminated RNA strands. Peptide 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.

Templates direct the sequence-specific anchoring of theC-terminus of peptido RNAs

“…The right-hand side of Scheme 1 lists the different products of the anchoring reactions with dipeptido dinucleotides (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). The results of reactions directed by different templates shed light on the effect of positioning of the dipeptido dinucleotides relative to the primer terminus.…”

Nitrogenous Derivatives of Phosphorus and the Origins of Life: Plausible Prebiotic Phosphorylating Agents in Water

“…Contrary to Orgel’s strategy, in this case the peptide formation took place from the N term to the C term and avoided the formation of diketopiperazine, which inhibits the oligomerization. The Richert group used “condensating buffers” containing N -(3-dimethylaminopropyl)- N ′-ethylcarbodiimide hydrochloride (EDC), carbonyl diimidazole (CDI) or cyanamide to couple the first amino acid with nucleotides to form the corresponding phosphoramidate 65 ( Figure 13 ) [ 54 , 55 , 56 ]. They also observed the formation of oligonucleotides 65 indicating a parallel phosphorylation of nucleotides.…”

Amino Acid‐Specific, Ribonucleotide‐Promoted Peptide Formation in the Absence of Enzymes

“…[25] Together with stereoelectronic and conformational factors,s uch as the rigidity of proline,i ntrinsic reactivity may thus provide the structural basis for whether peptido RNAs form efficiently or not. [25] Together with stereoelectronic and conformational factors,s uch as the rigidity of proline,i ntrinsic reactivity may thus provide the structural basis for whether peptido RNAs form efficiently or not.…”

“…Thel ow temperature and high salt concentration of our assays is reminiscent of eutectic phases, [24] and is favorable for folding of biomacromolecules. [3] Peptide formation in Nlinked form also accelerates chain growth over background oligomerization, as detailed in the accompanying paper, [25] so no enzymes are needed to start it. Because key molecules of encoding (RNA), catalysis (peptides), and metabolism (cofactors) are formed simultaneously,t his reactivity system may have been relevant for the earliest forms of life.…”