There has been a surge of recent interest, reflected by a sharp increase in the number of publications, in the area of high-resolution nuclear magnetic resonance (NMR) studies of DNA. The goal of many of these studies is to monitor the structure of biologically important DNA sequences directly in solution; the impetus for such studies was the realization, from early single-crystal X-ray structures, that nearest-neighbor context effects are a major determinant of local structure in short double-helical DNAs (Dickerson & Drew, 1981; Dickerson, 1983). Thus, instead of the previously assumed regular averaged structure of the double helix derived from fibre diffraction analysis, the more interesting concept emerged that specific sequence-dependent distortions from ‘classical’ DNA structure might be responsible for the recognition of such sequences by a variety of ligands such as repressors, polymerases, drugs, etc.

During the last twenty-five years the development of quantum mechanical calculations and experimental measurements of chemical shifts of the different type of nuclei present in nucleic acids have run parallel in close relation to each other. The first calculations dealt with intramolecular effects on base proton shifts (Veillard, 1962) but the real breakthrough of the theory occurred with the advent of computations of intermolecular shielding due to the ring current effect of the nucleic acid bases (Giessner-Prettre & Pullman, 1970).

Gramicidin A (GA) is a linear pentadecapeptide made of alternating D and L residues, in which the N-and C-terminals are blocked by a formyl group (head) and an ethanolamine end (tail), respectively (Sarges & Witkop, 1964):

The early NMR research on nucleic acids was of a qualitative nature and was restricted to partial characterization of short oligonucleotides in aqueous solution. Major advances in magnet design, spectrometer electronics, pulse techniques, data analysis and computational capabilities coupled with the availability of pure and abundant supply of long oligonucleotides have extended these studies towards the determination of the 3-D structure of nucleic acids in solution.

The microworld was revealed to investigators through a glass bead or a hanging water droplet long before optics was understood. The cellular structure of plants was well resolved by such simple magnifying glasses, van Leeuwenhoek, the Dutch merchant and amateur microscopist, was the first to report to the English Royal Society his observations of bacteria with his single-lens microscope in 1665.