Conformational states and biological activity of cyclic peptides

Nuclear magnetic resonance studies of the interaction of peptides and hormones with bovine neurophysin.

Ring current effects are the major source of conformation-dependent shifts observed in the 1H NMR spectrum of proteins, diamagnetic hemeproteins, or transfer RNAs. NMR spectroscopic techniques are nowadays capable of characterizing protein or transfer RNA spectra in great detail, especially in the case of small proteins (Campbell and Dobson, 1979). X-ray analyses of proteins or transfer RNAs have also attained sophisticated levels of crystallographic refinement in recent years (Blundell and Johnson, 1976; Artymiuk et al.,1979). Spectroscopic results can therefore be interpreted in terms of structural interactions based on the local environment of the aromatic ring in the macromolecule. These act as quite natural probes of the structure. Ring current concepts provide, directly or indirectly, a link between spectroscopy and structure in both static and dynamic aspects. Accordingly they constitute an invaluable key for appreciation of the significant biological properties of macromolecules from 1H NMR studies. This review chapter examines this role in detail, firstly to base this on the aromatic rings in proteins and then to extend this to transfer RNA. Since it is also the purpose of this chapter to assist the reader to see where ring current concepts can be applied, to perform his or her own calculations, and to be able to interpret ring current effects, details are given to facilitate this.

Application of Ring Current Calculations to the Proton NMR of Proteins and Transfer RNA

Determination of the solution conformations of cyclic polypeptides

The proton nuclear magnetic resonance spectra of metallothioneins from horse, human, and sheep livers were investigated. The spectra of the metallothioneins from the three species are similar as are the two isoproteins from any one species. The spectra indicate that metallothioneins possess a well-defined tertiary structure. Zinc(II) and calcium(II) ions induce similar but not identical tertiary structures. Confirmatory evidence was obtained for the involvement of cysteine residues in metal binding, but no evidence was obtained for the involvement of any other amino acid residue in metal binding. The apoprotein thionein was found to exist essentially in a random-coil conformation with perhaps some residual segmental structure.

Investigation of the structure of metallothioneins by proton nuclear magnetic resonance spectroscopy

The 220-MHz proton NMR spectra of lysine-vasopressin and some related compounds are examined in deuterated dimethyl sulfoxide to obtain structural information that must be satisfied by any proposed conformation of the molecule. This structural information is in the form of dihedral angles (for rotation about the NH-CαH bonds) from coupling constants, possible hydrogen bonding of the CONH2 and backbone amide groups from the temperature-dependence of the chemical shift, and aromatic ring-aromatic ring interaction from the effect of the magnetically anisotropic groups on the chemical shift.

H. A. Scheraga

Papers

Nuclear magnetic resonance studies of lysine-vasopressin: structural constraints.