The space structure of a conformationally labile oligopeptide in solution: angiotensin.

The paper describes a new approach to the problem of space structure description for conformationally labile molecules existing in solution as a set of different conformers in dynamic equilibrium. In such a case the "average" model derived exclusively from physico-chemical data represents a virtual structure devoid of physical sense. The proposed approach involves the selection of statistical weights wi for molecular conformers in solution by combined use of spectroscopic data and energy calculations (including the Monte-Carlo technique). Consequently, it appears possible to confine the entire region of all wi values only by those points (wi) that provide a reasonable agreement between the results of calculations and the experimental data. The approach was put to trial by using the linear octapeptide angiotensin, a well-known bioregulator with a wide spectrum of action. The 1H NMR and fluorescence spectroscopy were used as a source of experimental evidence concerning the space structure of the peptide in aqueous solution. The spin-lattice relaxation rates induced by the spin label allowed to estimate simultaneously several parameters characterizing the distance between the spin label and different functional groups in the angiotensin molecule. At least 5 types of angiotensin conformers were shown to be "indispensable" to achieve a good agreement between the results of energy calculations and 1H NMR spectroscopy data obtained in solution. The statistical weight estimates for angiotensin conformers permit to predict, with a high degree of accuracy, the value of singlet-singlet energy transfer between the Phe and Tyr aromatic chromophores of the molecule in aqueous solution. The proposed approach to the description of conformationally labile molecules can be actually regarded as stepwise refinement of statistical weight limits for sets of low-energy conformers in solution upon accumulation of new experimental evidence. The same appears to apply to conformationally labile molecules of non-peptide nature.

Equilibrium of conformers in solution: spin-labelled angiotensin.

The number of structural parameters were determined for spin-labelled angiotensin in aqueous solution with the use of fluorescence spectroscopy and 1H NMR relaxation induced by the spin label. At the same time all measured parameters were estimated theoretically by means of energy calculations and Monte-Carlo techniques. The matching procedure for experimental and computational data allows one to suggest a dynamic equilibrium between conformers of the molecule in aqueous solution and to estimate the values of their weights.