Short Oxoproline-Containing Peptides as Potential Pharmacological Means of Hypolipidemic and Antithrombotic Actions

Abstract

The search and research of pharmacological agents that could combine lipid-lowering and antithrombotic effects on the human organism are one of the most urgent and important tasks of modern biological and medical research. The unique effects of the regulatory peptides of the oxoproline series (5-охо-Pro- His-Pro-NH₂, 5-oxo-Pro-Trp-Pro, and 5-oxo-Pro-Arg-Pro or Pyr-His-Pro-NH₂, Pyr-Trp-Pro, and Pyr- Arg-Pro) synthesized by the methods of classical peptide chemistry have been found in animals with experimental hypercholesterolemia. Repeated intranasal administration of these peptides to animals with developed hypercholesterolemia increased their anticoagulant, fibrinolytic and antiplatelet potential of the blood and simultaneously lowered increased concentrations of total cholesterol, low-density lipoprotein cholesterol, and triglycerides. In addition, they promoted normalization of blood glucose. A week after the last administration of these peptides, the hypocholesterolemic, normoglycemic and anticoagulant effects persisted. The relationship between the structure of the oxoproline-containing peptides and their functional properties is discussed. It is concluded that further studies of oxoproline-containing peptides are promising in the context of development of pharmacological agents, combining the antithrombotic activity with the improvement of lipid metabolism in the body.