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Fragments of the Galanin Peptide and Their Synthetic Analogues with the Cardioprotective Effect

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Abstract

New peptide analogs of galanin corresponding to fragments of the N-terminal sequence were synthesized by an automatic solid-phase method using Fmoc-technology. Incomplete cleavage of the Boc-protection from the Trp indole ring was found during postsynthetic procedures and a method for solving this problem was proposed. Physicochemical properties of a number of natural and synthetic N-terminal fragments of galanin were been studied. A comparative evaluation of cardioprotective action of peptide agonists of the galanin GalR2 receptor was carried out on the model of the regional ischemia and reperfusion of the heart in rats in vivo. The analog that contained the carnosine sequence, H-Trp-Thr-Leu-Asn-Ser-Ala-Gly-Tyr-Leu-Leu-Gly-Pro-βAla-His-OH, was found to most effectively protect the heart from ischemic and reperfusion stress.

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Notes

  1. Reperfusion is a reestablishing of the blood flow to organs and tissues which earlier remained without the blood supply.

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Funding

This study was supported by the Russian Foundation for Basic Research, project nos. 18-015-00008 and 18-015-00009.

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Authors and Affiliations

  1. National Medical Research Center of Cardiology, Ministry of Health Care, 121552, Moscow, Russia

    M. E. Palkeeva, M. V. Sidorova, A. S. Molokoedov, M. V. Ovchinnikov, A. A. Az’muko, L. I. Serebryakova, O. M. Veselova, I. M. Studneva & O. I. Pisarenko

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

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All applicable international, national, and institutional guidelines for the care and use of animals were followed.

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Translated by L. Onoprienko

Abbreviations: Boc, tert-butyloxycarbonyl; DBU, 1,8–diazobicyclo[5.4.0]-undec-7-en; DCM, dichloromethane; DIPEA, N,N-diisopropylethylamine; DMA, N,N-dimethylacetamide; DMF, N,N-dimethylformamide; Fmoc, 9-fluorenylmethyloxycarbonyl; GalR, the galanin receptor; MALDI, the matrix-assisted laser desorption-ionization method; 4-MePip, 4-methylpiperidine; NMM, N-methylmorpholine; NMP, N-methylpyrrolidone; Pbf, 2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl; TBTU, N,N,N ',N '-tetramethyl-О-(benzotriazole-1-yl)uronium tetrafluoroborate; TFA, trifluoroacetic acid; Trt, trityl; RZ, the risk zone; MI, myocardiac infarction; CК-МВ, creatine kinase МВ; VS, ventriculus sinister (left ventricle of heart); RDА, the right descending artery; SBP, systolic blood pressure; SPS, the solid phase synthesis; HR, heart rate

Corresponding author: phone: +7 (495) 414-67-16; e-mail: peptide-cardio@yandex.ru.

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Palkeeva, M.E., Sidorova, M.V., Molokoedov, A.S. et al. Fragments of the Galanin Peptide and Their Synthetic Analogues with the Cardioprotective Effect. Russ J Bioorg Chem 45, 353–360 (2019). https://doi.org/10.1134/S1068162019040071

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