Construction and Assembly of Chimeric DNA: Oligonucleotide Hybrid Molecules Composed of Parallel or Antiparallel Duplexes and Tetrameric i‑Motifs

Chimeric DNA containing parallel (ps) and antiparallel (aps) duplex elements as well as poly-dC tracts were designed and synthesized. Oligonucleotide duplexes with ps chain orientation containing reverse Watson–Crick dA-dT base pairs and short d­(C)₂ tails are stabilized under slightly acidic conditions by hemiprotonated dCH⁺-dC base pairs (“clamp” effect). Corresponding molecules with aps orientation containing Watson–Crick dA-dT base pairs do not show this phenomenon. Chimeric DNA with ps duplex elements and long d­(C)₅ tails at one or at both ends assemble to tetrameric i-motif structures. Molecules with two terminal d­(C)₅ tails form multimeric assemblies which have the potential to form nanoscopic scaffolds. A preorganization of the ps duplex chains stabilizes the i-motif assemblies up to almost neutral conditions as evidenced by thermal melting and gel electrophoresis. Although, ps DNA is generally less stable than aps DNA, the aps duplexes contribute less to the stability of the i-motif than ps DNA