Conformational Nature of Monomeric Glucagon

It has been shown that monomeric glucagon in aqueous solution does not have a stable globular structure, the conformation changing continuously with change of temperature or concentration of denaturants added. Conformational and spectroscopic perturbations in the circular dichroism, induced by the effects of temperature and of denaturants, have been separated. A parallel study has been carried out on disuccinylglucagon, which has no detectable secondary structure as judged by circular dichroism and proton magnetic resonance analysis, and is not subject to the concentration-dependent conformation change characteristic of glucagon. This has allowed observation of the thermal and solvent perturbation of the random chain. The fluorescence has been examined and shows no significant difference from glucagon in respect of the extent of intramolecular excitation transfer, irrespective of pH. The nature of intramolecular interactions in glucagon is discussed. Three types of derivatives of glucagon each modified with chromophoric groups have been examined. Extrinsic Cotton effects have been observed, and in the case of the hydroxynitrobenzyl derivative, the transition to a highly associated state in acid solution still occurs, and is accompanied by an inversion in the system of Cotton effects associated with the extraneous chromophore.