EPIGENETIC EFFECT OF LYS-GLU AND ALA-GLU-ASP-GLY PEPTIDES ON HEMOSTASIS
It was found that dipeptide Lys-Glu and tetrapeptide Ala-Glu-Asp-Gly were able to normalize hemostasis in patients with severe hypercoagulation. Peptides interaction with promoter site of pro- and anticoagulants genes is supposed mechanism of this effect. GCAG sequence and its complementary sequence CGTC were binding sites located in tissue factor (TF) gene for dipeptide Lys-Glu, and CAAAG, CTTTA, CAAAT, GTTTC and CTTTA sequences were binding sites for tetrapeptide Ala-Glu-Asp-Gly. Binding sites in antithrombin III (AT-III) gene for tetrapeptide Ala-Glu-Asp-Gly were represented by ATTTC, GTTTC, TAAAG, CTTTA and CTTTG sequences, and for dipeptide Lys-Glu were represented only by GCAG, occurs once. In promoter region of protein C (PC) gene binding sites ATTTG, CAAAT, ATTTG were found for tetrapeptide Ala-Glu-Asp-Gly, and GCAG — for dipeptide Lys-Glu. Models of dipeptide and tetrapeptide molecular interaction with their selective binding sites were created. Normalizing effect of dipeptide Lys-Glu and tetrapeptide Ala-Glu-Asp-Gly on homeostasis in hypercoagulation condition can be associated with increased expression of natural anticoagulants genes (AT-III and PC) and suppression of TF gene.