[Spatial structure of angiotensin in an aqueous solution]. / Prostranstvennaia struktura angiotenzina v vodnom rastvore.

The spatial structure of spin-labeled angiotensin in aqueous solution wa investigated with the combined use of NMR, fluorescence spectroscopy and energy calculation including Monte-Carlo techniques. The calculated mean values of molecular parameters were compared with the experimental ones. The calculated and experimental mean values were regarded as statistically indistinguishable when the corresponding mean values occurred within the 95% confidence limit. The experimental parameters were shown to be adequately described by calculated conformers only with the assumption of the existence of dynamic equilibrium of conformers in solution. The mean values of statistical weights and their limits providing the agreement between the calculated and experimental data were determined. Two geometrically different forms of backbone structure for C-terminal hexapeptide in aqueous solution were revealed using the discussed approach; the N-terminal part of the molecule appeared to be much more conformationally labile. The model of molecule spatial structure is consistent with available literature data upon angiotensin titration experiments, its complexing with heavy metal ions etc.

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.

[Synthesis, biological activity and conformation of enkephalin analogs structurally related to kyotorphin]. / Sintez, biologicheskaia aktivnost' i konformatsionnye issledovaniia analogov énkefalina, strukturno rodstvennykh kiotrofinu.

[D-Arg2,Leu5]Enkephalin and two series of its N-terminal short-chain analogues with a free and modified C-terminal carboxylic group, viz. amides and ethyl esters of tri- and tetrapeptides, were synthesized in solution and by solid-phase method. Their analgesic activity, assayed by the "tail pinch" method following intracisternal and intravenous administration to mice, was compared with activity of enkephalins and morphine. To study the space structure of the synthesized compounds, conformational calculations and fluorescence spectroscopy were applied to measure distance between aromatic nuclei of tyrosine and phenylalanine residues in the two tetrapeptides. Ethyl esters of the tri- and tetrapeptides exceed in analgesic activity the corresponding carboxylic acids and amides. In contrast to the pentapeptide, the tetrapeptide analogues were active upon intravenous administration. Conformational aspects of this series of analogues are discussed in detail; the abrupt increase in activity upon transition from tri- to tetrapeptides does not appear to be related to conformational changes.

[Conformation of the enkephalin cycloanalog Lys-Tyr-Gly-Gly-Phe-Leu-]. / Prostranstvennaia struktura molekuly tsikloanaloga énkefalina Lys-Tyr-Gly-Gly-Phe-Leu-.

The spatial structure of an enkephaline cycloanalogue Lys-Tyr-Gly-Gly-Phe-Leu--has been investigated by means of energy calculations, fluorescence and CD-spectroscopy. Despite the high conformational mobility of the cycloanalogue, little resemblance exists between its and parent peptide's low-energy structures. Conformational factors for possible mechanisms of interaction between specific enkephalin receptors and cycloanalogue are discussed.