Thromboelastographic Research of Arginine-, Leucine and Lysine-Containing Peptides
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Bulletin of Experimental Biology and Medicine, Vol. 169, No. 6, October, 2020 PHARMACOLOGY AND TOXICOLOGY
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Thromboelastographic Research of Arginine-, Leucineand Lysine-Containing Peptides
E. Ya. Rogozinskaya1, L. A. Lyapina1, T. A. Shubina1, N. F. Myasoedov2, M. E. Grigorieva1, T. Yu. Obergan1, and L. A. Andreeva2 Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 169, No. 6, pp. 716-719, June, 2020 Original article submitted December 24, 2019 Anticoagulant effects of 12 short peptides of the glyproline series — Arg-Glu-Arg-Pro-GlyPro (RERPGP), Arg-Glu-Arg-Val-Gly-Pro (RERVGP), Arg-Glu-Arg-Gly-Pro (RERGP), Arg-Pro-Gly-Pro (RPGP), Pro-Leu-Pro (PLP), Pro-Leu-Pro-Ala (PLPA), Pro-Gly-Pro-Leu (PGPL), Phe-Pro-Leu-Pro-Ala (FPLPA), Pyr-Arg-Pro (PyrRP), Lys-Lys-Arg-Arg-Pro-GlyPro (KKRRPGP), Arg-Lys-Lys-Arg-Pro-Gly-Pro (RKKRPGP), and Lys-Arg-Lys-Pro-GlyPro (KRKPGP) in concentrations of 10—3 and 10—2 mg/ml in vitro was demonstrated by the thromboelastographic method. The effects of 6 peptides ((RERPGP, RPGP, PLP, PLPA, RKKRPGP, and KKRRPGP) were also observed in vivo after intranasal or oral administration. Changes in the studied thromboelastographic parameters towards hypocoagulation in comparison with the control group were noted. Arginine and leucine glyprolines produced the maximum anticoagulant effect. Key Words: glyprolines; thromboelastography; leucine-containing oligopeptides; argininecontaining oligopeptides; lysine-containing oligopeptides Regulatory oligopeptides of the glyproline series are produced in the body during collagen synthesis or degradation [2]. The PGP sequence is often found in the protein structure: types I, III, IV, and V collagens contain 28, 43, 25, and 44 PGP motifs, respectively [14]. Glyprolines are involved in the regulation of endothelial permeability [8], hemostasis [12], carbohydrate and lipid metabolism [13]. Their action is aimed at inhibiting blood coagulation due to the presence of anticoagulant properties [9]. Among glyprolines, leucine-, lysine- and arginine-containing oligopeptides are found. Arginine is extremely important, because it produces a wide range of therapeutic effects: hepatotropic, antimicrobial, immunotropic and psychotropic [4]. The presence of arginine in the glyproline structure increases anticoagulant activity of the peptide in vivo [9]. Leucine is involved in lipid and carbohydrate metabolism promoting utilization of lipids in mitoFaculty of Biology, M. V. Lomonosov Moscow State University, Moscow, Russia; 2Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia. Address for correspondence: [email protected]. E. Ya. Rogozinskaya
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chondria and reducing blood glucose levels [11]. This amino acid can affect protein synthesis in the liver and muscles and prevent overproduction of serotonin and the associated onset of fatigue [15]. Lysine is present in active centers of many proteins and hormones, e.g. thymosin α1 and thymopoietin, and is also present in CNS neurons brain [7]. The effect of peptides on the hemostasi
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