Efficient oligomerization of aromatic amino acids induced by gaps in four-helix bundles of DNA or RNA

Olivia Doppleb, Rainer Joachim Schwarz, Maria Landa and Clemens Richert

Chem Eur J https://doi.org/10.1002/chem.202104104

Abstract

The formation of peptides from amino acids is one of the processes associated with life. Because of the dominant role of translation in extant biology, peptide-forming processes that are RNA-induced are of particular interest. We had previously reported the formation of phosphoramidate-linked peptido RNAs as the products of spontaneous condensation reactions between ribonucleotides and free amino acids in aqueous solution. We now asked whether four-helix bundle (4HB) DNA or RNA folding motifs with a single- or double-nucleotide gap next to a 5'-phosphate can act as reaction sites for phosphoramidate formation. For glycine, this was found to be the case, whereas phenylalanine and tryptophan showed accelerated formation of peptides without a covalent link to the nucleic acid. Free peptides with up to 11 tryptophan or phenylalanine residues were found in precipitates forming in the presence of gap-containing DNA or RNA 4HB's. Control experiments using motifs with just a nick or primer alone did not have the same effect. Because folded structures with a gap in a double helix are likely products of hybridization of strands formed in statistically controlled oligomerization reactions, our results are interesting in the context of prebiotic scenarios. Independent of a putative role in evolution, our findings suggest that for some aromatic amino acids an RNA-induced pathway for oligomerization exists that does not have a discernable link to translation.