PNA-directed triple-helix formation by N7-xanthine

We report the first example of alkylation of underivatized xanthine with chloroacetic acid to yield a separable mixture of N-7- and N-9-(methylenecarboxyl)xanthine and its conversion to a peptide nucleic acid monomer compatible with Fmoc-based oligomerization chemistry. Additionally, we have simultaneously prepared the N-7- and N-9-PNA monomers of guanine by alkylation of 2-N-isobutyrylguanine which were subsequently separated. Molecular modeling of the nucleobase base triplets indicates that N-7-xanthine and N-7-guanine form isomorphous triplets with adenine and guanine, respectively. We also show that polyamides containing N-7-xanthine are compatible with triple-helix formation.