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Synthesis and Biological Properties of a New Dipeptide Mimetic of Brain-Derived Neurotrophic Factor Loop 2**

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Pharmaceutical Chemistry Journal Aims and scope

A dimeric dipeptide mimetic of brain-derived neurotrophic factor loop 2, bis-(N-hexanoyl-seryl-lysine) hexamethylenediamide or GTS-201, was designed and synthesized. It exhibited neuroprotective activity at concentrations of 10–5 – 10–8 M in HT-22 immortalized hippocampal neuronal cell culture under H2O2-induced oxidative stress. Western-blot analysis showed that it activated TrkB receptors and Erk but not Akt. GTS-201 did not exhibit antidepressant activity in a Porsolt forced swim test on BALB/c mice at i.p. doses of 0.1, 1.0, and 5.0 mg/kg, in contrast with previously synthesized GSB-106, a dimeric dipeptide mimetic of loop 4. The results confirmed the previous original hypothesis about the possible discrimination of neurotrophin functions by low-molecular-mass mimetics of their separate loops.

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References

  1. M. C. Cardenas-Aguayo, S. F. Kazim, I. Grundke-Iqbal, and K. Iqbal, PLoS One, 8(1), 1 – 18 (2013).

    Article  Google Scholar 

  2. C. Zuccato and E. Cattaneo, Nat. Rev. Neurol., 5, 311 – 322 (2009).

  3. H. Yu and Z. Chen, Acta Pharmacol. Sin., 32, 3 – 11 (2011).

  4. J. Adlam and R. Zaman, Psychiatr. Danubina, 25(2), 368 – 369 (2013).

    Google Scholar 

  5. B. C. Monteiro, S. Monteiro, M. Candida, et al., Clin. Pract. Epidemiol. Ment. Health, 13, 213 – 219 (2017).

  6. T. A. Gudasheva, T. A. Antipova, and S. B. Seredenin, Dokl. Akad. Nauk, 434(4), 549 – 552 (2010).

    Google Scholar 

  7. S. B. Seredenin and T. A. Gudasheva, RU Pat. 2,410,392, Aug. 27, 2010; Byull. Izobret., 3 (2011).

  8. T. A. Gudasheva, Izv. Akad. Nauk, Ser. Khim., 9, 2012 – 2021 (2015).

  9. T. A. Gudasheva, A. V. Tarasyuk, S. V. Pomogaibo, et al., Bioorg. Khim., 38(3), 280 – 290 (2012).

    CAS  PubMed  Google Scholar 

  10. S. B. Seredenin, T. A. Voronina, T. A. Gudasheva, et al., Acta Nat., 5(4), (19), 116 – 120 (2013).

  11. R. U. Ostrovskaya, S. S. Yagubova, T. A. Gudasheva, and S. B. Seredenin, Byull. Eksp. Biol. Med., 164(12), 701 – 705 (2017).

    Google Scholar 

  12. A. Paquet, Can. J. Chem., 60, 976 – 980 (1982).

  13. L. T. Kisfaludy, J. E. Roberts, R. H. Johnson, et al., J. Org. Chem., 35(10), 3563 – 3564 (1970).

    Article  CAS  Google Scholar 

  14. G. R. Jackson, K. Werrbach-Perez, E. L. Ezell, et al., Brain Res., 592(1), 239 – 248 (1992).

    Article  CAS  Google Scholar 

  15. R. D. Porsolt, A. Bertin, and M. Jalfre, Eur. J. Pharmacol., 51, 291 – 294 (1978).

  16. N. M. Sazonova, A. V. Tarasyuk, D. V. Kurilov, et al., Khim.-farm. Zh., 49(7), 10 – 19 (2015); Pharm. Chem. J., 49(7), 439 – 448 (2015).

  17. M. Jaouadi, J. Martinez, and B. Castro, J. Org. Chem., 52, 2364 – 2367 (1987).

  18. Y. Ueda, E. Walsh, H. Nakanishi, and K. Yoshida, Neurosci. Lett., 165(1 – 2), 203 – 207 (1994).

  19. S. M. Massa, T. Yang, Y. Xie, et al., J. Clin. Invest., 120(5), 1774 – 1785 (2010).

    Article  CAS  Google Scholar 

  20. J. Cassani, A. M. Dorantes-Barron, L. M. Novales, et al., Molecules, 19(12), 21442 – 21461 (2014).

    Article  Google Scholar 

Download references

Acknowledgments

The work was sponsored by the Russian Science Foundation (Project No. 18-15-00381).

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Authors and Affiliations

  1. V. V. Zakusov State Institute of Pharmacology, Russian Academy of Medical Sciences, 8 Baltiiskaya, Moscow, 125315, Russia

    N. M. Sazonova, A. V. Tarasyuk, A. N. Shumskii, P. Yu. Povarnina, S. V. Kruglov, T. A. Antipova, T. A. Gudasheva & S. B. Seredenin

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  1. N. M. Sazonova
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  2. A. V. Tarasyuk
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  3. A. N. Shumskii
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  4. P. Yu. Povarnina
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  5. S. V. Kruglov
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  6. T. A. Antipova
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  7. T. A. Gudasheva
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  8. S. B. Seredenin
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Corresponding author

Correspondence to N. M. Sazonova.

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** Published in part as academic theses; T. A. Gudasheva et al., Dokl. Akad. Nauk, 476(1), 108 – 112 (2017).

Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 52, No. 9, pp. 14 – 21, September, 2018.

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Sazonova, N.M., Tarasyuk, A.V., Shumskii, A.N. et al. Synthesis and Biological Properties of a New Dipeptide Mimetic of Brain-Derived Neurotrophic Factor Loop 2**. Pharm Chem J 52, 763–770 (2018). https://doi.org/10.1007/s11094-018-1896-0

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  • DOI: https://doi.org/10.1007/s11094-018-1896-0

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