Therapeutic oligonucleotides (ONs) are a new class of molecules that hold great promises to treat pathologies that cannot be cured with classical therapies. Their accurate characterization is critical for both the pharmaceutical industry and regulatory agencies.
In this whitepaper, we present the NMR characterization of a model therapeutic ON containing eight chemically modified nucleotide units and two phosphorothioate (PS) internucleotide linkages. Due to the presence of the R or S configurations at the PS linkages (designated as Rp and Sp) and to the lack of stereocontrol during conventional solid-phase synthesis, the 8-mer ON studied is in fact composed of a mixture of four diastereomers (2x PS linkages leading to 4 diastereoisomers).
