Guanine rich oligonucleotide–amino acid/peptide conjugates: preparation and characterization

Abstract

Covalent addition of aminoacyl or peptidyl groups could improve the performance of RNA/DNA molecules either in catalysis or in other attributes such as their ability to interact with membranes. This can explain the transformation of the RNA world first into a peptidyl-RNA world and eventually into a RNA–protein world. Subsequently, the emergence of DNA as more stable storage of genetic information than RNA finally gave shape to present day DNA–RNA–Protein world. For this reason, this paper reports a stepwise study, of the direct incorporation of amino acid/peptide onto synthetic amino modified deoxyoligonucleotide. The amino acid/peptide has been covalently linked to the primary amine of amino modified oligonucleotide, which is separated from the oligomer by a spacer arm of 10 atoms. The yield depends on the presence of bulky amino acid side chains that possibly hinder the attack of incoming nucleophile. On the other hand, the use of relatively high concentrations of EDC has improved the conjugation yield remarkably and complete conjugation can be achieved within few hours. Such a facile incorporation of amino acids or peptides may help oligonucleotides with greater cell membrane permeability, stability and reactivity.