Synthesis of a Peptidoyl RNA Hairpin via a Combination of Solid‐Phase and Template‐Directed Chain Assembly

Abstract

Dedicated to Ulf DiederichsenPeptidoyl RNAs are the products of ribosome-free, singlenucleotide translation. They contain a peptide in the backbone of the oligoribonucleotide and are interesting from a synthetic and a bioorganic point of view. A synthesis of a stabilized version of peptidoyl RNA, with an amide bond between the Cterminus of a peptide and a 3'-amino-2',3'-dideoxynucleoside in the RNA chain was developed. The preferred synthetic route used an N-Teoc-protected aminonucleoside support and in-volved a solution-phase coupling of the amino-terminal oligonucleotide to a dipeptido dinucleotide. Exploratory UVmelting and NMR analysis of the hairpin 5'-UUGGCGAAAGCdC-LeuLeu-AA-3' indicated that the peptide-linked RNA segments do not fold in a cooperative fashion. The synthetic access to doubly RNA-linked peptides on a scale sufficient for structural biology opens the door to the exploration of their structural and biochemical properties.

From RNA world to RNA-peptide world: A review

“…The presented results demonstrate how a combination of solid-phase chain assembly and template-directed peptide coupling in aqueous solution can prepare RNA-peptide hybrid molecules with the peptide embedded in the RNA backbone. This procedure can create peptidoyl RNAs with different sequences and chain lengths, allowing for the investigation of their chemical and structural characteristics and potential contributions to the prebiotic stage of evolution [23].…”