Parallel Double Stranded Helices and the Tertiary Structure of Nucleic Acids

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Abstract
Thermal denaturation of four oligonucleotides, viz. 3′-d(AT)5pO(CH2)6Opd(AT)5-3′ (par(AT)), 3′-d(AT)5pO(CH2)6Opd(AT)5-5′ (anti(AT))5 3′-d(A),opO(CH2)6Op(T),10-3′ (par(A-T)), and 3′- d(A) 10pO(CH2)6Opd(T)10-5′ (anti(A-T)), was studied in 0.01 M phosphate buffer, pH 7, in the presence of 0.1,0.25,0.5 and 1.0 M NaCl. All the oligomers were found to exist at a lower temperature (0 to 20°C) as complexes composed either of two oligomer molecules (a canonical duplex) or of more oligomer molecules whereas, at a higher temperature (30 to 70°C), they formed hairpins with a parallel (par(AT) and par(A-T)) or antiparallel (anti(AT) and anti(A-T)) orientation of the chains. Melting curves (A260(T)) were used to calculate thermodynamic parameters for the formation of hairpins and “low-temperature” duplexes. Experiments on ethidium bromide binding to the oligonucleotides have shown that the oligomer anti(A-T) exists, at a low ionic strength, as a four stranded complex (“quadruplex”) contains two antiparallel helices, d(A) · d(T), which have a parallel orientation and are bound to one another owing to the formation of additional hydrogen bonds between nucleic acid bases. The possible biological function of quadruplexes is discussed.