[Hypocoagulant effect of the novel dipeptide NGF mimetic GK-2]

The effect of an original dimeric dipeptide NGF mimetic, GK-2 (hexamethylenediamide bis-N-monosuccinyl-L-glutamyl-L-lysine, designed on the basis of the beta-turn of the 4th NGF loop) on the hemostasis and fibrinolysis was studied in intact and diabetic Wistar rats in various periods of disorder development. Model diabetes was induced by single streptozotocin (40 mg/kg i.p.) administration. Blood glucose level, main parameters of thromboelastograms, and euglobulin clot lysis time were measured. The effect of GK-2 was studied under ex vivo conditions, by adding freshly prepared peptide solution to the blood plasma. The maximum increase in the thrombosis probability was observed in ten days after streptozotocin injection, as manifested by an increase in coagulation indices CI and I together with a decrease in the euglobulin clot lysis time. Adding GK-2 (10(-5) M) to the blood plasma was found to normalize these parameters. The tendency to hypocoagulant effect was also observed in experiments with GK-2 adding to the blood plasma of intact animals. The hypocoagulant effect of GK-2 in combination with its antihyperglycemic effect (revealed previously) is of great importance, since diabetes is known to be accompanied by violated microcirculation and increased risk of thrombosis.