Human telomeric DNA: G‐quadruplex, i‐motif and Watson–Crick double helix

Human telomeric DNA composed of (TTAGGG/CCCTAA)n repeats may form a classical Watson–Crick double helix. Each individual strand is also prone to quadruplex formation: the G‐rich strand may adopt a G‐quadruplex conformation involving G‐quartets whereas the C‐rich strand may fold into an i‐motif based on intercalated C·C+ base pairs. Using an equimolar mixture of the telomeric oligonucleotides d[AGGG(TTAGGG)3] and d[(CCCTAA)3CCCT], we defined which structures existed and which would be the predominant species under a variety of experimental conditions. Under near‐physiological conditions of pH, temperature and salt concentration, telomeric DNA was predominantly in a double‐helix form. However, at lower pH values or higher temperatures, the G‐quadruplex and/or the i‐motif efficiently competed with the duplex. We also present kinetic and thermodynamic data for duplex association and for G‐quadruplex/i‐motif unfolding.