Choice of Problems in the Early Days of Biological NMR Spectroscopy

It was a mere ten years after the discovery of NMR that Oleg Jardetzky under the mentorship of the physical chemist John Wertz (Wertz and Jardetzky, 1956) began using 23Na NMR with the aim of studying Na+ transport in biological systems as suggested by William Lipscomb. Jardetzky found that Na+ NMR provided a unique method for following the binding of Na+ in weak complexes. Advantage was taken of the sensitivity of quadrupolar nuclei to their chemical environment as reflected in their relaxation rates which could be readily observed at a field of 7,030 gauss available at the time (Jardetzky and Wertz, 1956). From the very first, Jardetzky limited his choice to those problems that could be investigated uniquely or most effectively by NMR Spectroscopy. One of Jardetzky’s principal goals was to elucidate, at least in part, the threedimensional structures of biological macromolecules in aqueous solution, a distant goal in the late 1950’s. He realized that before attempting to tackle the structure of these complex molecules, proteins and nucleic acids, by NMR it was essential to initially characterize the spectra of their components, amino acids andnucleosides. In 1957, he published a note in the Journal of Chemical Physics (Takedaand Jardetzky, 1957) on a few amino acids, not only reporting the chemical shifts of all the protons but also showing that in a dipeptide, for example, glycylglycine, the two CH2 groups are non-equivalent. In 1958, he published an NMR paper, a systematic study of the proton NMR spectra of amino acids, in the Journal of Biological Chemistry (Jardetzky and Jardetzky, 1958), thus introducing many facets of NMR Spectroscopy to the biochemical community. This seminal paper included: l) the chemical shifts of the protons of 22 amino acids and their dependence on pH, concentration and ionic strength and 2) the effect of rate processes on the NMR spectrum as exemplified by the exchange of the guanidino protons of arginine with water. Increased structural information from peptide NMR spectroscopy attracted many investigators to this area of research.