Investigation of the effect of amino acid chirality in the internucleoside linker on DNA:DNA and DNA:RNA duplex stability

Enzymatically and chemically stable amide-linked di/oligonucleosides are highly desired synthetic targets in which the phosphodiester linkages in native DNA are replaced by amide linkers of appropriate length and stereochemistry. The five-atom amide-linked dimers, synthesized from 3′-amino-3′-deoxy thymidine, α-(l/d) proline/prochiral glycine and thymidine/uridine-4′carboxylic acid derivatives, were incorporated into the DNA backbone to achieve partial replacement of selected phosphodiester linkages. The results stressed the importance of the chirality of linker amino acid. d-Proline was found to be the most compatible as an internucleoside linker in the DNA backbone to stabilize the complexes with DNA or RNA as compared to l-proline and glycine.