Mixed Anhydride Intermediates in the Reaction of 5(4H)‐Oxazolones with Phosphate Esters and Nucleotides

Abstract

Abstract5(4H)‐Oxazolones can be formed through the activation of acylated α‐amino acids or of peptide C termini. They constitute potentially activated intermediates in the abiotic chemistry of peptides that preceded the origin of life or early stages of biology and are capable of yielding mixed carboxylic‐phosphoric anhydrides upon reaction with phosphate esters and nucleotides. Here, we present the results of a study aimed at investigating the chemistry that can be built through this interaction. As a matter of fact, the formation of mixed anhydrides with mononucleotides and nucleic acid models is shown to take place at positions involving a mono‐substituted phosphate group at the 3’‐ or 5’‐terminus but not at the internal phosphodiester linkages. In addition to the formation of mixed anhydrides, the subsequent intramolecular acyl or phosphoryl transfers taking place at the 3’‐terminus are considered to be particularly relevant to the common prebiotic chemistry of α‐amino acids and nucleotides.

Mapping a Systematic Ribozyme Fitness Landscape Reveals a Frustrated Evolutionary Network for Self-Aminoacylating RNA

“…These sites stand in contrast to the modification of modern tRNAs at the vicinal diol (3′ terminus), which is also found to be more reactive in model oligonucleotides. 43,44 It is possible that an internal reaction site facilitates establishment of multiple contacts with BYO, and the rate acceleration caused by these structural features outweighs the intrinsic reactivity of the vicinal diol. Similarly, it is unknown whether the identity of the 3′ terminal sequence (CUG in this study, compared to CCA in tRNAs) may contribute to this finding.…”

The Chemical Likelihood of Ribonucleotide-α-Amino acid Copolymers as Players for Early Stages of Evolution

“…To the best of our knowledge, the pioneering work of Shim et al (1974), mainly motivated by the identification of structures capable of template replication, an ability that was not confirmed later using closely related amide-based derivatives 2 (Zielinski and Orgel 1989), has not been investigated further. On the basis of our earlier experience in aminoacylation using α-amino acids strongly activated under the form of 5(4 H )-oxazolones and N -carboxyanhydrides (NCAs) (Liu et al 2014, 2016a, 2016b), we embarked on a study of potential prebiotic pathways of formation of phosphoramidate-linked adducts as well as of their hydrolytic stability. We now report the first results demonstrating that abiotic pathways for the formation of both ester and phosphoramidate key linkages of structure 1 are indeed available and that their kinetic stability is compatible with a role of chemical intermediates in a system based on amino acids and nucleotides predating the better established RNA–protein world.…”

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.…”

“…Classical work on the products of the mixed condensation of amino acids and ribonucleotides dates back to the 1950s, 11 and aspects of prebiotic chemistry of such condensation reactions have been explored in the past. 12,13 Pascal, Sutherland and colleagues have focused on cyclic intermediates in pathways to ribonucleotide-driven peptide syntheses, [14][15][16] Yarus and coworkers showed that short phenylalanine oligomers can form via ester chemistry, when the amino acid is preactivated as a mixed anhydride with adenosine monophosphate (AMP), in reactions of a tetranucleotide substrate catalyzed by a pentanucleotide ribozyme. 17,18 We have recently reported the spontaneous formation of 'peptido RNA' from a mixture of ribonucleotides and amino acids in aqueous condensation buffer.…”