Preclinical study of innovative peptides mimicking the tertiary structure of the α-helix B of erythropoietin

Autor: Ivan V. Golubev, Vladimir V. Gureev, Mikhail V. Korokin, Maria A. Zatolokina, Elena V. Avdeeva, Anastasia V. Gureeva, Il’ya S. Rozhkov, Elena A. Serdyuk, Valeriya A. Soldatova
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Research Results in Pharmacology, Vol 6, Iss 2, Pp 85-96 (2020)
Druh dokumentu: article
ISSN: 2658-381X
DOI: 10.3897/rrpharmacology.6.55385
Popis: Introduction: The aim of this study was to examine the effectiveness of innovative peptides obtained by addition of polypeptide motifs with antiaggregation activity (Arg-Gly-Asp, Lys-Gly-Asp and Pro-Gly-Pro) to a peptide mimicking the tertiary structure of the α-helix B of erythropoietin pHBSP (Pyr-Glu-Gln-Leu-Glu-Arg-Ala-Leu-Asn-Ser-Ser). Materials and methods: The cytoprotective activity of innovative peptides mimicking the tertiary structure of the α-helix B of erythropoietin at the doses of 5 μg/ml, 30 μg/ml and 50 μg/ml was studied on human endothelial cell culture in a simulated oxidative stress. An ADMA-like model of preeclampsia was simulated in the experiment. The study was conducted in 260 female Wistar rats, weighing 250–300 g. Results and discussion: Innovative peptides mimicking the tertiary structure of the α-helix B of erythropoietin retain their cytoprotective activity in a simulated oxidative stress in HUVEC cell culture at the doses of 5 μg/ml, 30 μg/ml, and 50 μg/ml. The compounds with laboratory codes P-αB1 and P-αB3 had the most pronounced cytoprotective activity. Administration of N-nitro-L-arginine-methyl ether to pregnant females for 7 days causes the morphofunctional changes similar to clinical changes in preeclampsia. The innovative peptide under laboratory code P-αB4 at the dose of 50 μg/kg mimicking the tertiary structure of the α-helix B of erythropoietin shows the most pronounced protective properties. Conclusion: Innovative peptides mimicking the tertiary structure of the α-helix B of erythropoietin have a pronounced positive influence on the morphofunctional disorders in animals with ADMA-like preeclampsia.
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