[Proteolysis of simple glyprolines by leucine aminopeptidase and enzymes from nasal slime, brain membranes, and rat blood].

Proteolysis of Pro-Gly-Pro-Leu, Pro-Gly-Pro-Gly and Pro-Gly-Pro were studied comparatively to Met-Glu-His-Phe-Pro-Gly-Pro (semax). It is shown that all three peptides are considerably more stable to proteolysis by N-leucine-aminopeptidase (EC 3.4.11.1, Sigma, type VI, 9.2 units/mg), and by enzymes of nasal slime, brain microsomal fractions, and rat blood. Metabolites of the proteolysis showed that semax derives His-Phe-Pro-Gly-Pro only, Pro-Gly-Pro-Leu forms Gly-Pro-Leu, Pro-Gly-Pro and Gly-Pro, Pro-Gly-Pro-Gly gives Pro-Gly-Pro and Gly-Pro, and Pro-Gly-Pro forms Gly-Pro.

[Proteolysis of semax analogues with different N-terminal amino acids by aminopeptidases].

Proteolysis of semax (Met-Glu-His-Phe-Pro-Gly-Pro, Sem) and its analogues ([Ala1]Sem, [Gly1]Sem, [Thr1]Sem, [Trp1]Sem) that are differ from semax in substitution of N-terminal Met residue were studied. It is shown that such replacement changes the rate of peptides degradation by N-aminopeptidases (EC 3.4.11.2, Sigma, Type VI, 9.2 units. Akt. / mg). [Ala1]Sem, [Gly1]Sem and [Thr1]Sem semax analogues proved to be more stable to proteolysis than semax (Sem), and their initial product of proteolysis is His-Phe-Pro-Gly-Pro (Sem-5). For triptophan analogue both Glu-His-Phe-Pro-Gly-Pro (Sem-6) and Sem-5 product are formed in similar quantities. It is found that all investigated analogues can be used as inhibitors in Sem proteolysis.

[Structural-functional study of glycine-and-proline-containing peptides (glyprolines) as potential neuroprotectors].

A synthetic scheme for preparation of (Gly-Pro)n, (Pro-Gly)n (n = 2, 3), and (Pro-Gly-Pro)n (n = 1, 2) peptides was elaborated. The effect of the synthesized peptides and the Gly-Pro and Pro-Gly dipeptides on survival of cultured cells of PC12 rat pheochromocytoma was studied under the conditions of oxidative stress induced by brief incubation of the cells with hydrogen peroxide. Peptides of the general formula (Gly-Pro)n and the Pro-Gly-Pro peptide at a concentration of 0.2-100 microM were shown to decrease the number of damaged cells. The Gly-Pro peptide was the most active and decreased the number of damaged cells by 49% on average at a concentration of 100 microM.

[Species and tissue distribution specificity of proteins binding 16alpha,17alpha-cycloalkane derivatives of progesterone]. / Vidovye i tkanevye osobennosti raspredeleniia belkov, sviazyvaiushchikh 16al'fa,17-al'fa-tsikoalkanovye proizvodnye progesterona.

The binding of [3H]progesterone and [3H] 16 alpha,17 alpha-cycloalkanoprogesterones to proteins from rat, rabbit, and human uteri and other organs was studied. We found that 16 alpha,17 alpha-cycloalkanoprogesterone derivatives display affinities for the uterine progesterone receptors comparable with that of the natural hormone and no substantial species differences in the affinity. Rabbit uterus was found to have no proteins distinct from the progesterone receptor that specifically bind [3H] 16 alpha,17 alpha-cycloalkanoprogesterones. At the same time, in the human uterus, we found another protein that binds some of these progesterone derivatives; it turned out to be similar to the protein from rat uterus. A similar protein with the same selectivity and affinity for steroids was also found in rat and human kidneys. Blood serum, liver, lung, and a number of other tissues were found to contain a protein of the third type that binds the same 16 alpha,17 alpha-cycloalkanoprogesterones and exhibits submicromolar Kd values for these steroids and a very low affinity for progesterone. We speculated that the introduction of a bulky substituent adjacently to the 17 beta-side chain of progesterone could result in a change in the general biodynamics of the derivative including its transport, uptake, and accumulation in tissues, which may determine the selectivity of its effect.

[Synthesis of tritium-labelled prostaglandin E1 and its binding to human platelets]. / Sintez mechennogo tritiem prostaglandina e1 i ego sviazyvanie s trombotsitami cheloveka.

A method has been developed that makes it possible to obtain [5,6-3H2]PGE1 with a yield of 35% and a molar radioactivity of 1.7-1.8 TBq/mmol. The binding of [5,6-3H2]PGE1 to native platelets proved to be specific, saturating and reversible. It is characterized by low values (approximately 10(-9) M) of dissociation constants for high-affinity sites, correlates with the inhibition of ADP-induced aggregation of platelets and can be considered as receptor binding. Specific binding of 10 +/- 2 molecules of PGE1 with one platelet was found to cause 50% inhibition of the ADP-induced aggregation.