English
Русский 37-47 p.
Biocompatible branched polymers can be used in many biomedical applications, including drug and gene delivery. In previous articles, we applied a computational approach to study complexes of positively charged lysine branched polymers and their complexes with some negatively charged regulatory oligopeptides. The goal of this article is to test the possibility of complex formation between peptide dendrimer and therapeutic oligopeptide molecules. A system consisting of one dendrimer, 16 oligopeptide molecules and counterions in water was studied by the molecular dynamics method. For this purpose, the Gromacs molecular modeling software package and the Amber force field were used. First of all, the process of complexation was studied and it was shown that negatively charged oligopeptide molecules are attracted by the dendrimer and quickly form a stable complex with it. After reaching a plateau of all characteristics of the complex, its average equilibrium dimensions, shape anisotropy, and internal structure were calculated. They turned out to be similar to the characteristics of the complexes formed by other branched lysine molecules with similar molecular weights and charges.
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19. Abraham M.J., Murtola T., Schulz R., Pall S., Smith J.C., Hess B. Lindahl E. GROMACS: High per-formance molecular simulations through multi-level parallelism from laptops to supercomputers. Software X 2015, 1-2, 19–25.
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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. Bi-ological 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 Positive-ly 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 pep-tide 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 La-beling 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 Deceler-ates Aging and Suppresses Development of Breast Adenocarcinomas in Transgenic HER-2/neu Mice. Bulle-tin of Experimental Biology and Medicine. – 2002, 134(2), 187-190.
16. Khavinson V.Kh., Malinin V.V. Gerontological aspects of genome peptide regulation, Basel (Switzer-land): 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 Mecha nism. 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 per-formance 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.