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

Abstract

Nucleic acids and polypeptides are at the heart of life. It is interesting to ask whether the monomers of these biopolymers possess intrinsic reactivity that favors oligomerization in the absence of enzymes. We have recently observed that covalently linked peptido RNA chains form when mixtures of monomers react in salt-rich condensation buffer. Here, we report the results of a screen of the 20 proteinogenic amino acids and four ribonucleotides. None of the amino acids prevent phosphodiester formation, so all of them are compatible with genetic encoding through RNA chain growth. A reactivity landscape was found, in which peptide formation strongly depends on the structure of the amino acid, but less on the nucleobase. For example, proline gives ribonucleotide-bound peptides most readily, tyrosine favors pyrophosphate and phosphodiester formation, and histidine gives phosphorimidazolides as dominant products. When proline and aspartic acid were allowed to compete for incorporation, only proline was found at the N-terminus of peptido chains. The reactivity described here links two fundamental classes of biomolecules through reactions that occur without enzymes, but with amino acid specificity.

Programmed Recognition between Complementary Dinucleolipids To Control the Self‐Assembly of Lipidic Amphiphiles

“…The field of systems chemistry is thus called on to provide key insights into the resolution of major open scientific questions, such as how life could emerge from inert matter and whether it is possible to engineer artificial life‐like processes and materials . Toward this goal, it is common to study the merging of different biological building blocks into synthetic systems with properties arising from the combination of their biomolecular components . This approach is normally based on self‐organization and/or chemistries that are dynamic in nature, and by looking closely at chiral effects of those components to reach specific morphologies .…”

“…[4][5][6][7] Toward this goal, it is common to study the merging of differentb iological buildingb locks into synthetic systems with properties arising from the combination of their biomolecular components. [8][9][10] Thisa pproach is normally based on self-organization and/or chemistries that are dynamic in nature, [11][12][13][14] and by looking closely at chiral effects of those components to reach specific morphologies. [15][16][17] The long-term goalo ft his strategy is to create chemical networks and assemblies with emergentproperties that are characteristicofl ife.…”

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.…”

“… The condensation of an amino acid 35 and a 5'-nucleoside monophosphate 62 in a condensing buffer leading to the simultaneous formation of oligonucleotides and oligopeptides amino acid 5'-nucleoside amidophosphate [ 54 , 55 , 56 ]. …”