Convergent Synthesis of the Rat Galanin and Study of Its Biological Activity

• Published in: Russian journal of bioorganic chemistry 2020, Vol.46 (1), p.32-42
• Main Authors: Sidorova, M. V., Palkeeva, M. E., Avdeev, D. V., Molokoedov, A. S., Ovchinnikov, M. V., Azmuko, A. A., Serebryakova, L. I., Veselova, O. M., Studneva, I. M., Pisarenko, O. I.
• Format: Article
• Language: English
• Subjects: Adenine; Adenosine triphosphate; Biochemistry; Biological activity; Biomedical and Life Sciences; Biomedicine; Bioorganic Chemistry; Blood plasma; Creatine; Glycine; Injury prevention; Kinases; Lactate dehydrogenase; Life Sciences; Myocardial infarction; Necrosis; Nucleotides; Organic Chemistry; Peptides; Solid phases; Synthesis
• ISSN: 1068-1620; 1608-330X
• DOI: 10.1134/S1068162020010100

The full-length rat galanin (GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH 2 , G29) was prepared by the solid phase peptide synthesis using the Fmoc-strategy. The peptide chain was elongated both by one amino acid and by a fragment condensation. Fragments with the C -terminal glycine residue were synthesized by the solid phase method on the 2-chlorotrityl chloride resin or by the method of conventional peptide synthesis in solution. After the reversed phase HPLC, galanin had the correct molecular weight and 98% purity. We studied the G29 cardioprotective properties on a model of acute myocardial infarction in rats. The G29 administration reduced the infarct size by 40% and decreased the activity of necrosis markers CK-MB (Creatine Kinase-MB) and LDH (Lactate Dehydrogenase) in the blood plasma. The peptide improved metabolic state of the infarcted heart, increased the ATP content, the total adenine nucleotide pool, phosphocreatine, and total creatine, and decreased the lactate level compared to a control. These results indicated the possibility of the G29 use as a drug for reducing the myocardial reperfusion injury. In addition, the mechanisms of the G29 action should be studied.