Баку, Азербайджан
Баку, Азербайджан
В представленной работе исследовано пространственное и электронное строение наиболее низкоэнергетической конформации N1H таутомера карнозина в цвиттерионной форме, имеющего широкий спектр применения. Расчеты проводились квантовохимическим методом DFT на основе гибридного функционала B3LYP и базисного набора 6-31+G(d,p) в газе, воде и в ДМСО с использованием программ Gaussian 09 и GaussView 6.0.16. Вычислены геометрические параметры, значения электронной энергии, дипольные моменты, величины парциальных зарядов на атомах, энергии HOMO и LUMO орбиталей, дескрипторы реакционной способности молекулы и проведен NBO анализ. Визуализированы карты молекулярного электростатического потенциала (МЕР) и граничные орбитали, Проанализированы структурные и электронные перестройки в молекуле и изменения различных параметров в зависимости от диэлектрической проницаемости среды. Выявлено, что влияние растворителя не играет существенной роли для данной структуры, получены очень похожие результаты для водной среды и ДМСО. Однако в газовой фазе оптимизация геометрии данного таутомера цвиттериона карнозина привела к отщеплению атома водорода от концевой группы NH3+ и присоединению его к группе СОО-, фактически преобразовав цвиттерионную форму в нейтральную.
цвиттерион карнозина, структура, глобальные дескрипторы реактивности, NBO анализ, ИК спектры
1. Boldyrev A.A., Aldini G., Derave W. Physiology and pathophysiology of carnosine. Physiol Rev., 2013, vol. 93, pp. 1803-1845, doi:https://doi.org/10.1152/physrev.00039.2012.
2. Болдырев А.А. Проблемы и перспективы исследования биологической роли карнозина. Биохимия, 2000, т. 65, № 7, с. 884-890.
3. Hipkiss A.R. Chapter 3: Carnosine and Its Possible Roles in Nutrition and Health. Advances in Food and Nutrition Research., 2009, vol. 57, pp. 87-154, doi: 10.1016 / S1043-4526 (09) 57003-9.
4. Gallant S., Kukley M., Stvolinsky S., Bulygina E., Boldyrev A. Effect of carnosine on rats under experimental brain ischemia. Tohoku J. Exp. Med., 2000, vol. 191, pp. 85-99, doi:https://doi.org/10.1620/tjem.191.85.
5. Prokopieva V.D., Yarygina E.G., Bokhan N.A., Ivanova S.A. Use of carnosine for oxidative stress reduction in different pathologies. Oxid Med Cell Longev., 2016, no. 29390872016, doi:https://doi.org/10.1155/2016/2939087.
6. Caruso G., Fresta C.G. et al. Carnosine prevents Aβ-induced oxidative stress and inflammation in microglial cells: A key role of TGF-β1. Cells, 2019, vol. 8, no. 1, pp. 64-86, doi:https://doi.org/10.3390/cells8010064.
7. Wu G. Important roles of dietary taurine, creatine, carnosine, anserine and 4-hydroxyproline in human nutrition and health. Amino Acids, 2020, vol. 52, no. 3, pp. 329-360, doi:https://doi.org/10.1007/s00726-020-02823-6.
8. Hipkiss A.R. COVID-19 and Senotherapeutics: Any Role for the Naturally-occurring Dipeptide Carnosine? Aging Dis., 2020, vol.11, no. 4, pp. 737-741, doi:https://doi.org/10.14336/AD.2020.0518.
9. Saadah L.M., Deiab G.I.A., Al-Balas Q., Basheti I.A. Carnosine to Combat Novel Coronavirus (nCoV): Molecular Docking and Modeling to Cocrystallized Host Angiotensin-Converting Enzyme 2 (ACE2) and Viral Spike Protein. Molecules, 2020, vol. 25, no. 23, pp. 5605-5619, doi:https://doi.org/10.3390/molecules25235605.
10. Diniz F.C., Hipkiss A.R., Ferreira G.C. The Potential Use of Carnosine in Diabetes and Other Afflictions Reported in Long COVID Patients. Front Neurosci., 2022, vol. 16, p. 898735, doi:https://doi.org/10.3389/fnins.2022.898735.
11. Bennet S., Kaufmann M. et al. Small-molecule metabolome identifies potential therapeutic targets against COVID-19. Sci Rep., 2022, vol. 12, no. 1, p. 10029, doi:https://doi.org/10.1038/s41598-022-14050-y.
12. Caruso G. Unveiling the Hidden Therapeutic Potential of Carnosine, a Molecule with a Multimodal Mechanism of Action: A Position Paper. Molecules, 2022, vol. 27, no. 10, p. 3303, doi:https://doi.org/10.3390/molecules27103303.
13. Matsukura T., Tanaka H. Applicability of Zinc Complex of L-Carnosine for Medical Use. Biochemistry (Mosc.), 2000, vol. 65, no. 7, pp. 817-823.
14. Jain S., Kim E.S. et al. Comparative cerebroprotective potential of d- and l-carnosine following ischemic stroke in mice. Int. J. Mol. Sci., 2020, vol. 21, no. 9, pp. 3053-3065, doi:https://doi.org/10.3390/ijms21093053.
15. Zhao J., Posa D.K. et al. Carnosine protects cardiac myocytes against lipid peroxidation products. Amino Acids, 2019, vol. 51, no. 1, pp. 123-138, doi:https://doi.org/10.1007/s00726-018-2676-6.
16. Petersmann A., Müller-Wieland D. et al. Definition, Classification and Diagnosis of Diabetes Mellitus. Exp. Clin. Endocrinol. Diabetes., 2019, vol. 127, iss. S01, pp. S1-S7, doi:https://doi.org/10.1055/a-1018-9078.
17. Riedl E., Pfister F. et al. Carnosine prevents apoptosis of glomerular cells and podocyte loss in STZ diabetic rats. Cell Physiol Biochem., 2011, vol. 28 no 2, pp. 279-288, doi:https://doi.org/10.1159/000331740.
18. Peters V., Zschocke J., Schmitt C.P. Carnosinase, diabetes mellitus and the potential relevance of carnosinase deficiency. J Inherit Metab Dis., 2018, vol. 41, no. 1, pp. 39-47, doi:https://doi.org/10.1007/s10545-017-0099-2.
19. Kiliś-Pstrusińska K. Carnosine, carnosinase and kidney diseases. Postepy Hig Med Dosw, 2012, vol. 66, pp. 215-221.
20. Zhao J., Shi L., Zhang L.-R. Neuroprotective effect of carnosine against salsolinol-induced Parkinson's disease. Exp. Ther. Med., 2017, vol. 14, no. 1, pp. 664-670, doi:https://doi.org/10.3892/etm.2017.4571.
21. Calon F., Cole G. Neuroprotective action of omega-3 polyunsaturated fatty acids against neurodegenerative diseases: evidence from animal studies. Prostaglandins Leukot Essent Fatty Acids, 2007, vol. 77, no. 5-6, pp. 287-293, doi:https://doi.org/10.1016/j.plefa.2007.10.019.
22. Bermúdez M L., Seroogy K.B., Genter M.B. Evaluation of carnosine intervention in the Thy1-aSyn mouse model of Parkinson's disease. Neuroscience, 2019, vol. 411, pp. 270-278, doi:https://doi.org/10.1016/j.neuroscience.2019.05.026.
23. Gaunitz F., Hipkiss A.R. Carnosine and cancer: a perspective. Amino Acids, 2012, vol. 43, no. 1, pp. 135-142, doi:https://doi.org/10.1007/s00726-012-1271-5.
24. Oppermann H., Faust H., Yamanishi U., Meixensberger J., Gaunitz F. Carnosine inhibits glioblastoma growth independent from PI3K/Akt/mTOR signaling. PLoS ONE, 2019, vol. 14, no. 6, e0218972, doi:https://doi.org/10.1371/journal.pone.0218972.
25. Shen Y., Yang J., Li J., Shi X., Ouyang L., Tian Y., Lu J. Carnosine inhibits the proliferation of human gastric cancer SGC-7901 cells through both of the mitochondrial respiration and glycolysis pathways. PLoS ONE, 2014, vol. 9, no. 8, e104632, doi:https://doi.org/10.1371/journal.pone.0104632.
26. Zhang Z., Miao L., Wu X., Liu G., Peng Y., Xin X., Jiao B., Kong X. Carnosine inhibits the proliferation of human gastric carcinoma cells by retarding Akt/mTOR/p70S6K signaling. J. Cancer., 2014, vol. 5, pp. 382-389. doi:https://doi.org/10.7150/jca.8024.
27. Lee J., Park J.R., Lee H., Jang S., Ryu S.M., Kim H., Kim D., Jang A., Yang S.R. L-carnosine induces apoptosis/cell cycle arrest via suppression of NF-κB/STAT1 pathway in HCT116 colorectal cancer cells. In Vitro Cell Dev Biol Anim., 2018, vol. 54, pp. 505-512, doi:https://doi.org/10.1007/s11626-018-0264-4.
28. Hsieh S.-L., Li J.-H., Dong C.-D., Chen C.-W., Wu C.-C. Carnosine suppresses human colorectal cancer cell proliferation by inducing necroptosis and autophagy and reducing angiogenesis. Oncol Lett., 2022, vol. 23 no. 2, p. 44, doi:https://doi.org/10.3892/ol.2021.13162.
29. Chuang C.-H., Hu M.-L. L-Carnosine Inhibits Metastasis of SK-Hep-1 Cells by Inhibition of Matrix Metaoproteinase-9 Expression and Induction of an Antimetastatic Gene, nm23-H1. Nutr Cancer, 2008, vol. 60, no. 4, pp. 526-533, doi:https://doi.org/10.1080/01635580801911787.
30. Hsieh S.-L., Hsieh S., Lai P.-Y., Wang J.-J., Li C.-C., Wu C.-C. Carnosine suppresses human colorectal cell migration and intravasation by regulating EMT and MMP expression. Am J Chin Med, 2019, vol. 47, no. 2, pp. 477-494, doi:https://doi.org/10.1142/s0192415x19500241.
31. Wu C.-C, Lai P.-Y, Hsieh S., Cheng C.-C., Hsieh S.-L. Suppression of carnosine on adhesion and extravasation of human colorectal cancer cells. Anticancer Res., 2019, vol. 39, no. 11, pp. 6135-6144, doi:https://doi.org/10.21873/anticanres.13821.
32. Rybakova Y. S., Boldyrev A. A., Effect of Carnosine and Related Compounds on Proliferation of Cultured Rat Pheochromocytoma PC-12 Cells. Bull. Exp. Biol. Med., 2012, vol. 154, no. 1, pp. 136-140, doi:https://doi.org/10.1007/s10517-012-1894-2.
33. Hipkiss A.R., Baye E., de Courten B. Carnosine and the processes of ageing. Maturitas, 2016, vol. 93, pp. 28-33, doi:https://doi.org/10.1016/j.maturitas.2016.06.002.
34. Cararo J.H., Streck E.L., Schuck P.F., da C. Ferreira G. Carnosine and Related Peptides: Therapeutic Potential in Age-Related Disorders. Aging and Disease, 2015, vol. 6, no. 5, pp. 369-379, doi:https://doi.org/10.14336/AD.2015.0616.
35. Kawahara M., Tanaka K.-I., Kato-Negishi M. Zinc, Carnosine, and Neurodegenerative Diseases. Nutrients, 2018, vol. 10, no. 2, pp. 147-167, doi:https://doi.org/10.3390/nu10020147.
36. Shao L., Li Q., Tan Z. L-Carnosine reduces telomere damage and shortening rate in cultured normal fibroblasts. Biochemical and Biophysical Research Communications, 2004, vol. 324, no. 2, pp. 931-936, doi:https://doi.org/10.1016/j.bbrc.2004.09.136.
37. Rashid I., van Reyk D.M., Davies M.J. Carnosine and its constituents inhibit glycation of low-density lipoproteins that promotes foam cell formation in vitro. FEBS Lett., 2007, vol. 581 no. 5, pp. 1067-1070, doi:https://doi.org/10.1016/j.febslet.2007.01.082.
38. Caruso G., Fresta C.G. et al. Carnosine Counteracts the Molecular Alterations Aβ Oligomers-Induced in Human Retinal Pigment Epithelial Cells. Molecules, 2023, vo. 28, pp. 3324-3338, doi:https://doi.org/10.3390/molecules28083324.
39. Демухамедова С.Д. Теоретическое квантово-химическое моделирование структуры и свойств дипептида карнозина методом DFT. Aктуальные вопросы биологической физики и химии, 2022, т. 7, № 2, c. 241-250, doi:https://doi.org/10.29039/rusjbpc.2022.0509.
40. Akverdieva G.A., Alieva I.N., Hajiyev Z.I., Demukhamedova S.D. Spatial structure of N1H and N3H tautomers of carnosine in zwitterion form. AJP Fizika, 2021, vol. XXVII, no. 2, section: En, 2021, pp. 29-37.
41. Baran E.J. Metal complexes of carmnosine. Biochemistry, 2000, vol. 65, no.7, pp. 789-797.
42. Frisch M.J. et al. Gaussian 09, Revision D.01, Gaussian, Inc., Wallingford CT, 2013.
43. Dennington R., Keith T., Millam J. Gauss View, Version 6.0.16. Shawnee, Kansas: Semichem Inc., Shawnee Mission, 2016.
44. Itoh H., Yamane T., Ashida T. Carnosine (-Alanyl-L-histidine). Acta Cryst., 1977, vol. B33, pp. 2959-2961, doi:https://doi.org/10.1107/S0567740877009972.
45. Koopmans T. Über die Zuordnung von Wellenfunktionen und Eigenwerten zu den Einzelnen Elektronen Eines Atoms. Physica, 1934, vol. 1, no. 1-6, pp. 104-113, doi:https://doi.org/10.1016/s0031-8914(34)90011-2.
46. Weinhold F., Landis C.R. Valency and Bonding: A Natural Bond Orbital Donor-Acceptor Perspective. Cambridge University Press, 2005.
