Separation of "uncharged" oligodeoxynucleotide analogs by anion-exchange chromatography at high pH.

Ion-exchange chromatography is a well-established method for the analysis and purification of phosphodiester-linked oligonucleotides (1). If elution is carried out under alkaline conditions, the secondary structure of Gand C-rich oligomers is disrupted. Furthermore, elution times become more sensitive to the G and T content of the oligomer, because G and T are deprotonated at pH 10 (2). In recent work on peptide-nucleic acids (PNAs) 1 we noted that mixtures of PNA oligomers G4, G_, Gs, and Gjo are readily separated by elution at pH 12 on an RPC-5 column (3). Here we show that this separation method is more generally applicable. The sequences of the oligomers of the type PNA-Lys-