The three-dimensional structures of proteins are among the most valuable contributions of biophysics to the understanding of biological systems (Dickerson & Geis, 1969; Creighton, 1983). Protein structures are utilized in the description and interpretation of a wide variety of biological phenomena, including genetic regulation, enzyme mechanisms, antibody recognition, cellular energetics, and macroscopic mechanical and structural properties of molecular assemblies. Virtually all of the information currently available about the structures of proteins at atomic resolution has been obtained from diffraction studies of single crystals of proteins (Wyckoff et al, 1985). However, recently developed NMR methods are capable of determining the structures of proteins and are now being applied to a variety of systems, including proteins in solution and other non-crystalline environments that are not amenable for X-ray diffraction studies. Solid-state NMR methods are useful for proteins that undergo limited overall reorientation by virtue of their being in the crystalline solid state or integral parts of supramolecular structures that do not reorient rapidly in solution. For reviews of applications of solid-state NMR spectroscopy to biological systems see Torchia and VanderHart (1979), Griffin (1981), Oldfield et al. (1982), Opella (1982), Torchia (1982), Gauesh (1984), Torchia (1984) and Opella (1986). This review describes how solid-state NMR can be used to obtain structural information about proteins. Methods applicable to samples with macroscopic orientation are emphasized.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0033583500004017

Protein structure by solid-state NMR spectroscopy.

▪ Abstract During the past decade, blind analysis has become a widely used tool in nuclear and particle physics measurements. A blind analysis avoids the possibility of experimenters biasing their result toward their own preconceptions by preventing them from knowing the answer until the analysis is complete. There is at least circumstantial evidence that such a bias has affected past measurements, and as experiments have become costlier and more difficult and hence harder to reproduce, the possibility of bias has become a more important issue than in the past. We describe here the motivations for performing a blind analysis, and give several modern examples of successful blind analysis strategies.

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Blind Analysis in Nuclear and Particle Physics

The theoretical background and experimental implementation of overtone NMR spectroscopy of quadrupolar nuclei, i.e., the direct observation of NMR signals at multiples of the Larmor frequency, are described. Perturbation theory is used to derive expressions for the dependence of overtone NMR frequencies, transition moments, and dipole–dipole splittings on molecular orientation for a nucleus with arbitrary spin. Experimental techniques for overtone cross‐polarization and for two‐dimensional spectroscopic measurements of transition moments and dipole–dipole splittings are demonstrated with 14N overtone spectra of single crystals. Overtone powder pattern line shapes are analyzed, both for spin S=1 and spin S=3/2 nuclei, and examples of 14N overtone powder patterns are presented. Overtone spectroscopy can be used to characterize quadrupole and dipole–dipole interactions in polycrystalline samples. The sensitivity, resolution, and spectral width characteristics of overtone NMR spectra are discussed and contrasted with those of conventional NMR spectra. The sensitivity and resolution of overtone spectra are shown to be comparable to those of conventional spectra, while the reduced spectral width of overtone spectra is a significant advantage in studies of single crystals and, in particular, polycrystalline materials.

Overtone NMR spectroscopy

NMR-NQR studies of structural phase transitions

521 useful primarily for its review of the functional anatomy of the lymphoid system given by Fabrikant. Indeed, the main value of the volume rests in its reviews and in the variety of techniques employed so that it may prove a useful reference source. It is perhaps a pity that one has to wait until the mid point of the meeting to read Mendlesohn's assessment of the cell cycle in malignant and normal tissues. In this excellent review both the technology of cell kinetics experimentation and comparisons of cell behaviour are brought out very strongly and it is recommended that the reader turns first to this article. Frindel, Dethlefsen and Valeriote all present overall studies of cell proliferation under radiation or drug treatments leading to a rational design of cancer therapeutic procedures. Valeriote, however, is wise in recognizing cell population kinetics as only one of about two dozen factors and the purpose of his review is to put cell cycle analysis in tumour therapy in its proper perspective. Again it is a pity that this paper comes so late in the proceedings. Much legitimate concern is shown by a number of authors over the problems created by studying asynchronously proliferating populations of cells which have a random age and mixed chemical composition. They accordingly resort to artificially synchronized populations (mainly in vitro) in the anticipation of obtaining relevant information before the cells become, once more, asynchronous. The reader may take his choice and chance on any of a number of techniques for producing cell proliferative synchrony. Such conditions were commonly used for the biochemical observations and several authors demonstrate a marked cyclicity of enzyme and cyclic AMP levels related to phases of the cell cycle. To the non-biochemist, this group of papers can provide a quick reference point to such biochemical intricacies as, for example, cyclic AMP metabolism and poly-amine biosynthesis. An analytical essay on mitotic control in the body is presented by Cameron and liberally supported with examples. He cites three levels of control: (i) general, affecting all proliferative populations, (2) specific, for certain organs, tissues or populations and (3) local action between cells of the same population. This article removes the blinkers that have occasionally beset this type of work and makes essential reading for a student 36 of cell proliferation control. Regrettably he omits consideration of a fourth type of control, namely local action between cells of …

A Review of Cyclophosphamide

14 N nuclear quadrupole resonance in the ferroelectric phase of sodium nitrite

Nuclear quadrupole resonance in 5-membered heterocycles: Pyrazole, imidazole, 1, 2, 4-triazole

14N nuclear quadrupole resonance (NQR) spectra of 22 monosubstituted anilines are reported and analyzed in the framework of the Townes and Dailey theory. Satisfactory correlations of the NQR data with both the Hammett σ parameters and the in vitro biological activities of the corresponding sulfanilamides have been found. The results obtained suggest that the nitrogen lone-pair orbital is more sensitive than the nitrogen–carbon sigma orbital is to substituent effects.

14N nuclear quadrupole resonance study of substituted anilines and prediction of in vitro activity of sulfanilamides

Nuclear quadrupole resonance in C-nitro compounds

Nitrogen-14 nuclear quadrupole resonance (NQR) spectra of nicotinic acid derivatives, known as antitumor agents, are reported and analyzed in the framework of the Townes and Dailey theory. A strong correlation exists between the charge difference σNC − π at the pyridinic nitrogen and the inhibition of acetylcholinesterase by nicotinic acid derivatives, in which the inhibition potency (pI50) increases as the charge difference σNC − π increases. There are significant differences between 14N NQR spectra for the pyridinic nitrogen sites of nicotinic acid and nicotinamide; these can be explained in terms of the differences in hydrogen bond lengths.

P.J. Bray

Papers

14 N nuclear quadrupole resonance in the ferroelectric phase of sodium nitrite

Nuclear quadrupole resonance in 5-membered heterocycles: Pyrazole, imidazole, 1, 2, 4-triazole

14N nuclear quadrupole resonance study of substituted anilines and prediction of in vitro activity of sulfanilamides

Nuclear quadrupole resonance in C-nitro compounds

14N nuclear quadrupole resonance in nicotinic acid derivatives