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Биосовместимые разветвленные полимеры могут быть использованы во многих биомедицинских приложениях, включая доставку лекарств и генов. В предыдущих статьях мы применили вычислительный подход для изучения комплексов положительно заряженных лизиновых разветвленных полимеров с некоторыми отрицательно заряженными регуляторными олигопептидами. Целью данной статьи является проверка возможности образования комплекса пептидным дендримером и молекулами терапев-тического олигопептида. Система, состоящая из одного дендримера, 16 молекул олигопептида и контрионов в воде была исследована методом молекулярной динамики. Для этой цели использовались пакет программ молекулярного моделирования Gromacs и силовое поле Amber. В первую очередь был изучен процесс комплексообразования и было показано, что отрицательно заряженные молекулы олигопептида притягиваются дендримером и быстро образуют с ним стабильный комплекс. После выхода на плато всех характеристик комплекса были рассчитаны его равновесные размеры, анизотропия формы и внутренняя структура. Они оказалась сходными, с размерами комплексов, образованных другими разветвленными лизиновыми молекулами, имеющими сходные молекулярные массы и заряды.
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14. Sheveleva N.N., Markelov D.A., Vovk M.A., Tarasenko I.I., Mikhailova, M.E. Stable Deuterium Labeling of Histidine-Rich Lysine-Based Dendrimers. Molecules 2019, 24, 2481, doi:10.3390/molecules24132481.
15. Anisimov V.N., Khavinson V.Kh., Alimova I.N., Semchenko A.V., Yashin A.I. Epithalon Decelerates Aging and Suppresses Development of Breast Adenocarcinomas in Transgenic HER-2/neu Mice. Bulletin of Experimental Biology and Medicine. – 2002, 134(2), 187-190.
16. Khavinson V.Kh., Malinin V.V. Gerontological aspects of genome peptide regulation, Basel (Switzerland): Karger AG, 2005. – 104 p.
17. Khavinson V., Diomede F., Mironova E., Linkova N., Trofimova S., Trubiani O., Caputi S., Sijari B. AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Posible Epigenetic Mechanism. Molecules. 2020, 25(3) 609.
18. Anisimov V.N., Khavinson V.Kh., Popovich I.G., Zabezhinski M.A., Alimova I.N., Rosenfeld S.V., Zavarzina N.Yu., Semenchenko A.V., Yashin A.I. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology 2003, 4, 193-202.
19. Abraham M.J., Murtola T., Schulz R., Pall S., Smith J.C., Hess B. Lindahl E. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. Software X 2015, 1-2, 19–25.
20. Lindorff-Larsen K., Piana S., Palmo K., Maragakis P., Klepeis J.L., Dror R.O., Shaw D.E. Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins 2010, 78, 1950–1958.
21. Okrugin B., Ilyash M., Markelov D., Neelov I. Lysine dendrigraft nanocontainers. influence of topology on their size and internal structure, Pharmaceutics 2018, 10 (3), 129.
22. Darinskii A.A., Zarembo A., Balabaev N.K., Neelov I.M., Sundholm F. Anisotropy of diffusion in a liquid crystalline system of semi-flexible polymer chains, Physical Chemistry Chemical Physics 2003, 5 (11), 2410-2416.
23. Shavykin O., Mikhailov I., Darinskii A., Neelov I., Leermakers F. Effect of an asymmetry of branching on structural characteristics of dendrimers revealed by Brownian dynamics simulations. Polymer 2018, 146, 256–266.
24. Shavykin O.V., Leermakers F.A., Neelov I.M., Darinskii A.A. Self-Assembly of Lysine-Based Dendritic Surfactants Modeled by the Self-Consistent Field Approach. Langmuir 2018, 34, 1613–1626.
2. Polcyn P. Zielinska P., Zimnicka, M., Troc A., Kalicki P., Solecka J., Laskowska A., Urbanczyk-Lipkowska Z. Novel antimicrobial peptide dendrimers with amphiphilic surface and their interactions with phospholipids – Insights from mass spectrometry. Molecules 2013, 18, 7120–7144.
3. Klajnert B., Janiszewska J., Urbanczyk-Lipkowska Z., Bryszewska M., Shcharbin D., Labieniec M. Biological properties of low molecular mass peptide dendrimers. Int. J. Pharm. 2006, 309, 208–217.
4. Sadler K., Tam J.P. Peptide dendrimers: Applications and synthesis. Rev. Mol. Biotechnol. 2002, 90, 195–229.
5. Tam J. Synthetic peptide vaccine design: Synthesis and properties of a high-density multiple antigenic peptide system. Proc. Natl. Acad. Sci. USA 1988, 85, 5409–5413.
6. Luo, K., Li C., Li L., She W., Wang G., Gu, Z. Arginine functionalized peptide dendrimers as potential gene delivery vehicles. Biomaterials 2012, 33, 4917–4927.
7. Lee H., Choi J.S., Larson R.G. Molecular Dynamics Studies of the Size and Internal Structure of the PAMAM Dendrimer Grafted with Arginine and Histidine. Macromolecules 2011, 44, 8681–8686.
8. Sheikhi Mehrabadi F., Zeng H., Johnson M., Schlesener C., Guan Z., Haag R., Multivalent dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection. Beilstein J.Org. Chem. 2015, 11, 763–772.
9. Filipe L.C.S., Machuqueiro M., Darbre T., Baptista A.M. Exploring the Structural Properties of Positively Charged Peptide Dendrimers. The Journal of Physical Chemistry B 2016, 120, 11323–11330.
10. Sheveleva N.N., Markelov D.A., Vovk M.A., Mikhailova M.E. Tarasenko I.
NMR studies of excluded volume interactions in peptide dendrimers. Scientific reports 2018, 8, 8916. doi:10.1039/c9ra02461a
11. Gorzkiewicz M., Konopka M., Janaszewska A., Tarasenko I.I. Application of new lysine-based peptide dendrimers D3K2 and D3G2 for gene delivery: Specific cytotoxicity to cancer cells and transfection in vitro. Bioorg. Chem. 2020, 95, 103504. doi: 10.1016/j.bioorg.2019.103504.
12. Sheveleva N.N. Markelov D.A., Vovk M.A., Mikhailova M.E., Tarasenko I Lysine-based dendrimer with double arginine residues. RSC Adv. 2019, 9, 18018–18026, doi:10.1039/c9ra02461a
13. Gorzkiewicz M., Kopec O., Janaszewska A., Konopk M., Pedziwiatr-Werbicka E., Tarasenko I.I. Poly(lysine) Dendrimers Form Complexes with siRNA and Provide Its Efficient Uptake by Myeloid Cells: Model Studies for Therapeutic Nucleic Acid Delivery. Int. J. Mol. Sci. 2020, 21, 3138, doi:10.3390/ijms21093138.
14. Sheveleva N.N., Markelov D.A., Vovk M.A., Tarasenko I.I., Mikhailova, M.E. Stable Deuterium Labeling of Histidine-Rich Lysine-Based Dendrimers. Molecules 2019, 24, 2481, doi:10.3390/molecules24132481.
15. Anisimov V.N., Khavinson V.Kh., Alimova I.N., Semchenko A.V., Yashin A.I. Epithalon Decelerates Aging and Suppresses Development of Breast Adenocarcinomas in Transgenic HER-2/neu Mice. Bulletin of Experimental Biology and Medicine. – 2002, 134(2), 187-190.
16. Khavinson V.Kh., Malinin V.V. Gerontological aspects of genome peptide regulation, Basel (Switzerland): Karger AG, 2005. – 104 p.
17. Khavinson V., Diomede F., Mironova E., Linkova N., Trofimova S., Trubiani O., Caputi S., Sijari B. AEDG Peptide (Epitalon) Stimulates Gene Expression and Protein Synthesis during Neurogenesis: Posible Epigenetic Mechanism. Molecules. 2020, 25(3) 609.
18. Anisimov V.N., Khavinson V.Kh., Popovich I.G., Zabezhinski M.A., Alimova I.N., Rosenfeld S.V., Zavarzina N.Yu., Semenchenko A.V., Yashin A.I. Effect of Epitalon on biomarkers of aging, life span and spontaneous tumor incidence in female Swiss-derived SHR mice. Biogerontology 2003, 4, 193-202.
19. Abraham M.J., Murtola T., Schulz R., Pall S., Smith J.C., Hess B. Lindahl E. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. Software X 2015, 1-2, 19–25.
20. Lindorff-Larsen K., Piana S., Palmo K., Maragakis P., Klepeis J.L., Dror R.O., Shaw D.E. Improved side-chain torsion potentials for the Amber ff99SB protein force field. Proteins 2010, 78, 1950–1958.
21. Okrugin B., Ilyash M., Markelov D., Neelov I. Lysine dendrigraft nanocontainers. influence of topology on their size and internal structure, Pharmaceutics 2018, 10 (3), 129.
22. Darinskii A.A., Zarembo A., Balabaev N.K., Neelov I.M., Sundholm F. Anisotropy of diffusion in a liquid crystalline system of semi-flexible polymer chains, Physical Chemistry Chemical Physics 2003, 5 (11), 2410-2416.
23. Shavykin O., Mikhailov I., Darinskii A., Neelov I., Leermakers F. Effect of an asymmetry of branching on structural characteristics of dendrimers revealed by Brownian dynamics simulations. Polymer 2018, 146, 256–266.
24. Shavykin O.V., Leermakers F.A., Neelov I.M., Darinskii A.A. Self-Assembly of Lysine-Based Dendritic Surfactants Modeled by the Self-Consistent Field Approach. Langmuir 2018, 34, 1613–1626.