The involvement of nitric oxide in the responses of the hemostasis system to the appearance of proline-containing peptides in the blood was studied in experiments on rats. It was shown that a single ...intranasal administration of peptides PGP, RPGP, and PGPL to rats led to an increase in fibrinolytic, anticoagulant, and antiplatelet potential of blood. The use of the non-selective NO-synthase blocker L-NAME almost completely inhibited the anticoagulant effects of the glyprolines. It was found that the mechanism of the anticoagulant-fibrinolytic and antiplatelet action of glyproline peptides is determined by the activation of the enzymatic pathway of nitric oxide formation. The obtained results revealed the involvement of nitric oxide in the implementation of hemostatic and vascular-endothelial functions of the organism.
The effect of temperature on the effectiveness of the incorporation of deuterium into pyrrolylcarnosine (PC) was studied. Deuterium gas and heavy water were used as a source of deuterium. Isotope ...exchange was carried out using solid-phase and liquid-phase methods. It was found that it is better to use isotope exchange with deuterated water to obtain preparative amounts of labeled pyrrolylcarnosine. When using y solid-phase method, the main label is in pyrrole. The incorporation of deuterium at a higher temperature occurs more evenly. In addition, the use of deuterated water made it possible to reduce the amount of unlabeled isotopomer to almost 0% and to obtain a product with a yield of 70% and a content of more than seven deuterium atoms. It was established that the content of deuterium in the compound can be increased by pretreating the reaction mixture with deuterium gas. This approach opens up additional opportunities for the synthesis of labeled compounds.
The importance of studying the action mechanisms of drugs based on natural regulatory peptides is commonly recognized. Particular attention is paid to the peptide drugs that contribute to the ...restoration of brain functions after acute cerebrovascular accidents (stroke), which for many years continues to be one of the main problems and threats to human health. However, molecular genetic changes in the brain in response to ischemia, as well as the mechanisms of protective effects of peptides, have not been sufficiently studied. This limits the use of neuroprotective peptides and makes it difficult to develop new, more efficient drugs with targeted action on brain functions. Transcriptome analysis is a promising approach for studying the mechanisms of the damaging effects of cerebral ischemia and neuroprotective action of peptide drugs. Beside investigating the role of mRNAs in protein synthesis, the development of new neuroprotection strategies requires studying the involvement of regulatory RNAs in ischemia. Of greatest interest are microRNAs (miRNAs) and circular RNAs (circRNAs), which are expressed predominantly in the brain. CircRNAs can interact with miRNAs and diminish their activity, thereby inhibiting miRNA-mediated repression of mRNAs. It has become apparent that analysis of the circRNA/miRNA/mRNA system is essential for deciphering the mechanisms of brain damage and repair. Here, we present the results of studies on the ischemia-induced changes in the activity of genes and peptide-mediated alterations in the transcriptome profiles in experimental ischemia and formulate the basic principles of peptide regulation in the ischemia-induced damage.
We studied the effects of Selank on intestinal microbiota in Wistar male rats subjected to chronic restraint stress. Selank was injected intraperitoneally in doses of 80, 250 and 750 μg/kg 15 min ...before stress exposure. Chronic restraint stress led to a decrease in the content of obligate microflora, while the content of opportunistic microorganisms increased. Selank restored intestinal microbiota presumably via central (neurotropic) and peripheral (immunotropic) mechanisms.
The efficiency of isotopic exchange using a homogeneous base (Et
3
N) and heterogeneous catalysts is compared. Deuterated water was used as the deuterium source. The incorporation of deuterium into ...ouabain reached on average about 3.26 atoms but the yield was limited to 15 – 20% if Et
3
N was used. It was found that 5% Pd/BaSO
4
was best for obtaining preparative amounts of labeled ouabain. A preparation with a yield of 77% and an average content of 2.14 deuterium atoms per molecule was obtained when the reaction was carried out at 125ºC for 30 min. The use of heterogeneous catalysts simplified the purification of the final product since the number of by-products was noticeably lower than when Et
3
N was used.
The influence of various factors on the efficiency of introducing deuterium into 3-(
N
-pyrrolyl)-propanoyl-L-histidine and 3-(
N
-salicyl)-propanoyl-L-histidine was studied. Heavy water was used as ...a source of deuterium. It is shown that the content of deuterium atoms in the substance can be increased by pretreating the reaction mixture with deuterium gas. The new approach opens up additional possibilities both for obtaining high labeled pharmaceuticals by introducing hydrogen isotopes into organic compounds, and theoretically for a deeper understanding of the role in this process of activated deuterium or tritium particles solvated on the carrier and in the pool of matter.
Effect of temperature on the efficiency of deuterium introduction into a new biologically active compound salicylcarnosine (SC) has been studied. Gaseous deuterium and heavy water were used as ...deuterium sources. The synthesis of labelled SC by a solid-phase method at 190°C leads to formation of DSC in 53% yield and deuterium content about 4.8 atoms per molecule. It has been shown that isotope exchange between SC protons and deuterium water proceeds more efficiently after preliminary treatment of catalyst with gaseous deuterium at ambient temperature. DSC forms in 46% yield and contains about 7.3 deuterium atoms per molecule. The preparative synthesis of labelled SC by this procedure at 190°C results in DSC yield of 60–70% at deuterium content about 6.2 atoms per molecule. The new procedure for the activation of deuterium inclusion in peptides opens additional opportunities for preparing highly labelled compounds.
Objective:
The resistance of carnosine, pyrrolylcarnosine (PC) and salicylcarnosine (SC) to the action of leucine aminopeptidase and carboxypeptidases B and Y was evaluated.
Methods:
Proteolysis of ...carnosine and its derivatives under the action of leucine aminopeptidase, carboxypeptidases Y and B, or under the action of enzyme systems of plasma membranes of rat brain cells or blood plasma.
Results and Discussion:
It was found that proteolysis of carnosine, PC and SC under the action of leucine aminopeptidase does not occur. Carboxypeptidases B and Y, as well as the enzyme systems of blood plasma and plasma membranes of rat brain cells, degraded peptides containing β-alanyl,
N
-pyrrolyl,
N
-salicylic fragments to varying degrees. In all cases, histidine was formed. The formation of pyrrole or salicylic acid did not occur.
Conclusions:
It was found that carnosine, PC and SC showed high resistance to the action of amino- and carboxypeptidases in
in
vitro
experiments.
The efficiency of isotope exchange was compared when gaseous deuterium (solvent-free, solid-phase exchange) and deuterium water were employed as a deuterium source. It was established that exchange ...with deuterium water is preferable for producing labeled β-alanyl-L-histidine. When using the solid-phase method, the main part of the label is in histidine. The distribution of deuterium during isotope exchange with D
2
O is more uniform. In addition, the use of deuterium water makes it possible to reduce the amount of unlabeled isotopomer to 0.4% and receive a preparation with a yield of 40% (20 mg) and an average content of 3.6 deuterium atoms per carnosine molecule. It can be assumed that the high yield and greater incorporation of deuterium are associated with the pretreatment of the reaction mixture with gaseous deuterium.
