M. J. J. Blommers

High Resolution NMR Studies of DNA Hairpins with Four Nucleotides in the Loop Region

Abstract When considering DNA structure the first picture that comes to mind is that of the celebrated double helix. Notwithstanding the overwhelming importance of this structure it is interesting however that refined structural studies that have been conducted during the last ten years have demonstrated that deviations, at the nucleotide level, from the idealized double helix and its consonant symmetry properties may lead to very interesting global structural variations.

Conformational Aspects of Hairpin Loops in DNA Oligonucleotides

Our studies (2–5) towards the structure, kinetics and thermodynamics of DNA hairpins formed in solution by the homologous, (partly-) selfcomplementary DNA fragments d (ATCCTATnTAGGAT), n=0-7, showed that the inherent stability of DNA hairpins is at its maximum when the loop of the hairpin comprises four or five nucleotides. This finding is at variance with earlier experiments (6) which indicated that in RNA hairpins loop lengths of six to seven residues are the most favourable.

NMR Studies of Loopfolding in a DNA Hairpin Molecule

The last decade has witnessed an outburst of NMR studies of nucleic acid structure and dynamics. Initially such investigations were aimed at the study of exchange properties of imino protons involved in hydrogen bonding in basepairs, at the determination of the melting properties of double helical molecules and at resolving the conformational properties of the sugar moieties in small oligonucleotides. Detailed structural studies were hampered by the inability to interpret the complicated spectra which are obtained for medium sized and larger nucleic acid molecules. In the last five years this situation has changed dramatically. The introduction of NMR spectrometers operating at 500 MHz and the development of two dimensional Fourier Transform methods have increased the resolution of the NMR method tremendously. The concommitant development of assignment procedures and the possibility to measure short range distances, albeit in a qualitative way, between protons in a molecule, have made the NMR technique one of the most powerful methods to study the structure of molecules in solution.