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

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Abstract

The full-length rat galanin (GWTLNSAGYLLGPHAIDNHRSFSDKHGLT-NH2, 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.

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Funding

This study was supported by the Russian Foundation for Basic Research, project no. 18-015-00009).

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Authors and Affiliations

  1. National Medical Research Cardiological Center, Russian Ministry of Health, 121552, Moscow, Russia

    M. V. Sidorova, M. E. Palkeeva, D. V. Avdeev, A. S. Molokoedov, M. V. Ovchinnikov, A. A. Azmuko, L. I. Serebryakova, O. M. Veselova, I. M. Studneva & O. I. Pisarenko

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  1. M. V. Sidorova
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  2. M. E. Palkeeva
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  3. D. V. Avdeev
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  4. A. S. Molokoedov
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  5. M. V. Ovchinnikov
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  6. A. A. Azmuko
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  7. L. I. Serebryakova
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  8. O. M. Veselova
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  9. I. M. Studneva
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  10. O. I. Pisarenko
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Correspondence to M. V. Sidorova.

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COMPLIANCE WITH ETHICAL STANDARDS

This article does not contain any studies involving human participants performed by any of the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

CONFLICT OF INTERST

The authors declare that they have no conflicts of interest.

Additional information

Translated by L. Onoprienko

Abbreviations: Boc, tert-butyloxycarbonyl; Bzl, benzyl; DCM, dichloromethane; DIEA, N,N-diisopropylethylamine; DIC, N,N-diisopropylcarbodiimide; Fmoc, 9-fluorenylmethoxycarbonyl; GalR, the galanin receptor; MALDI, the matrix-assisted laser desorption-ionization mass spectrometry; 4-MePip, 4‑methylpiperidine; NMM, N-methylmorpholine; NMP, N‑methylpyrrolidone; HONSu, N-hydroxysuccinimide; Pbf, 2,2,4,6,7-pentamethyldihydrobenzofurane-5-sulfonyl; TIS, triisopropylsilane; TFA, trifluoroacetic acid; Tos, tosyl; Trt, trityl; RZ, the risk zone; Z, benzyloxycarbonyl; MI, the myocardial infarction; Cr, creatine; CК-МВ, creatine kinase MB; LV, the left ventricle; RDA, the right descending artery; SAP, systolic arterial pressure; SPS, the solid phase synthesis; PCr, phosphocreatine; HR, heart rate.

Corresponding author: phone: +7(495)4146716; e-mail: peptide-cardio@yandex.ru.

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Sidorova, M.V., Palkeeva, M.E., Avdeev, D.V. et al. Convergent Synthesis of the Rat Galanin and Study of Its Biological Activity. Russ J Bioorg Chem 46, 32–42 (2020). https://doi.org/10.1134/S1068162020010100

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