PNA-Directed Triple-Helix Formation by N7-Xanthine

Abstract 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.