Conformational interpretation of intramolecular electron transfer in Met5-enkephalins between Tyr and Met(S:.Br) radical.

Mean distances between C beta atoms of redox centers and mean values of the exponentially distance dependent rate constants for intramolecular electron transfer, (k), in aqueous solution were calculated for Met5-enkephalin and its D-Ala2 analogue using the molecular mechanics and Monte Carlo techniques. The ratio of (k) values thus obtained proved similar to that determined experimentally for intramolecular electron transfer accompanying Met(S:.Br)----TyrO.radical transformation in these two peptides. This agreement indicates that the almost 2-fold difference observed between experimental k values for Met5-enkephalin and its D-Ala2 analogue can be attributed to the effect of Gly2 for D-Ala2 replacement on the average separation of the redox centers.

Dynamic space structure of the Leu-enkephalin molecule in DMSO solution.

The dynamical space structure of the Leu-enkephalin molecule in DMSO solution was described combining the ROE measurements and Monte Carlo energy calculations. The statistical weights for possible Leu-enkephalin conformers were estimated by comparing the NMR-experimental parameters and the same parameters average over statistical samples of molecular structures obtained by Monte Carlo techniques for every low-energy conformer. The statistical weight estimations reveal that the Leu-enkephalin molecule in DMSO solution is apparently represented by a mixture of at least two peptide backbone conformers with the mean statistical weight values of 70% and 30%. Both conformers possess significant local conformational fluctuations. Each of them represents a folded backbone structure with the folding at the Gly2-Gly3 and Gly3-Phe4 fragments occurring simultaneously in solution.

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.

Combined use of spectroscopic and energy calculation methods for the determination of peptide conformation in solution.

This paper describes the combined use of energy calculations and spectroscopic data for the determination of peptide conformations in solution. The approach involves (i) experimental measurements of spectroscopic parameters for a molecule, (ii) calculation of these parameters for low-energy conformers previously determined with regard to local fluctuations in conformation and (iii) a random search for statistically weighted combinations of conformers which provide a good agreement between the calculated and experimental data. The above approach was used to study the conformation of a spin-labelled angiotensin molecule (SL-AT). It appears that the C-terminal hexapeptide of SL-AT possesses two geometrically different spatial forms of the backbone in aqueous solution, with mean values for the statistical weight of 0.78 and 0.22, respectively. In contrast, the N-terminal part of the molecule is conformationally labile. The data obtained can be used to describe the conformation of angiotensin in solution.

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.

Conformational aspects of antiviral activity of deoxyguanosine acyclic analogues.

Conformational possibilities of a series of deoxyguanosine analogues possessing or lacking antiviral activity were evaluated using methods of the molecular mechanics. Comparison of the spatial structures of acyclic analogues with one another and with the spatial structures of deoxyguanosine demonstrates restricted conformational mobility for compounds devoid of activity. The level of sterically allowed superposition of functional groups from the acyclic moieties of analogues and the corresponding atomic centres of deoxyribose could serve as a criterion of activity. The superposition could be performed in two different ways through either of the nonhydrogen substituents at the C1' atom in the five-membered ring.