The possibility of complex formation by short lysine brush and therapeutic Semax peptides was investigated using molecular dynamics method. Lysine dendrimers and polymer brushes are used for drug and other (e.g., DNA, peptides, and polysaccharides) molecules delivery to different target cells. It is known that they could penetrate blood brain barrier. Since short lysine brush is nontoxic, a system containing of such brush and 8 oppositely charged Semax peptides was studied. It was obtained that stable complexes consisting of brush and peptides formed and structures of these complexes were investigated. Such complex can be used in future for delivery of Semax peptides to brain since these peptides have significant antioxidant, antihypoxic and neuroprotective effects.
KeywordsLysine BrushSemax PeptidesComputer SimulationMethod of Molecular Dynamics
Frechet, J.M.J. and Tomalia, D.A. (2001) Dendrimers and Other Dendriric Polymers. John Wiley & Sons Ltd., West Sussex. https://doi.org/10.1002/0470845821
Denkewalter, R.G., Kolc, J. and Lukasavage, W.J. (1983) Macromolecular Highly Branched Homogeneous Compound. US Patent No. 4410688.
Lee, C.C. and Fréchet, J.M.J. (2006) Synthesis and Conformations of Dendronized Poly-L-Lysine. Macromolecules, 39, 476-481. https://doi.org/10.1021/ma052078b
Cottet, H., Martin, M., Papillaud, A., Souaid, E., Collet, H. and Commeyras, A. (2007) Determination of Dendrigraft Poly-L-Lysine Diffusion Coefficients by Taylor Dispersion Analysis. Biomacromolecules, 8, 3235-3243. https://doi.org/10.1021/bm070268j
Collet, H., Souaid, E., Cottet, H., Dératani, A., Boiteau, L., Dessalces, G., Rossi, J.-C., Commeyras, A. and Pascal, R. (2010) Expeditious, Multigram Scale Synthesis of Lysine Dendrigraft (DGL) Polymers by Aqueous N-Carboxyanhydride Polycondensation. Chemistry: A European Journal, 16, 2309-2316. https://doi.org/10.1002/chem.200901734
Rossi, J.-C., Boiteau, L., Collet, H., Tsamba, B.M., Larcher, N. and Pascal, R. (2012) Functionalisation of Free Amino Groups of Lysine Dendrigraft (DGL) Polymers. Tetrahedron Letters, 53, 2976-2979. https://doi.org/10.1016/j.tetlet.2012.03.082
Oukacine, F., Romestand, B., Goodall, D.M., Massiera, G., Garrelly, L. and Cottet, H. (2012) Study of Antibacterial Activity by Capillary Electrophoresis Using Multiple UV Detection Points. Analytical Chemistry, 84, 3302-3310. https://doi.org/10.1021/ac300004t
Cadiere, A., Couturaud, B., Boismard, J., Le Cann, P., Gerard, A., Mas, A., Faye, C., Garrelly, L. and Roig B. (2013) Assessment of Poly-L-Lysine Dendrigrafts for Virus Concentration in Water: Use of MS2 Bacteriophage as Proof of Concept. Journal of Applied Microbiology, 115, 290-297. https://doi.org/10.1111/jam.12209
Li, J., Guo, Y., Kuang, Y., An, S., Ma, H. and Jiang, C. (2013) Choline Transporter-Targeting and Co-Delivery System for Glioma Therapy. Biomaterials, 34, 9142-9148. https://doi.org/10.1016/j.biomaterials.2013.08.030
Shypshyna, M.S., Veselovsky, N.S., Myasoedov, N.F., Shram, S.I. and Fedulova, S.A. (2015) Effect of Peptide Semax on Synaptic Activity and Short-Term Plasticity of Glutamatergic Synapses of Co-Cultured Dorsal Root Ganglion and Dorsal Horn Neurons. Fiziologicheskiî Zhurnal, 61, 48-55.
Popova, E.V., Shavykin, O.V., Neelov, I.M. and Leermakers, F. (2016) Molecular Dynamics Simulation of Lysine Dendrimer and Semax Peptides Interaction. Scientific and Technical Journal of Information Technologies, Mechanics and Optics, 16, 716-724. https://doi.org/10.17586/2226-1494-2016-16-4-716-724
Alder, B.J. and Wainwright, T.E. (1957) Molecular Dynamics by Electronic Computers. In: Prigogine, I., Ed., International Symposium on Transport Processes in Statistical Mechanics, John Wiley Int., New York, 97-131.
Verlet, L. (1967) Computer “Experiments” on Classical Fluids. I. Thermodynamical Properties of Lennard-Jones Molecules. Physical Review, 159, 98-103. https://doi.org/10.1103/PhysRev.159.98
Rahman, A. and Stillinger, F.H. (1972) Mollecular Dynamics Study of Temperature Effects on Water Structure and Kinetics. Journal of Chemical Physics, 57, 1281-1292. https://doi.org/10.1063/1.1678388
Balabaev, M.N.K., Grivtsov, A.G. and Shnol, E.E. (1972) Numerical Modeling of Motion of Molecules. Motion of Isolated Polymer Chain. Institute of Applied Mathematics, 4, 38.
Ryckaert, J.P., Ciccotti, G. and Berendsen, H.V.C. (1977) Numerical Integration of Cartesian Equations of Motion of Systems with Constraints-Molecular Dynamics of N-Alkanes. Journal of Computational Physics, 23, 327-341. https://doi.org/10.1016/0021-9991(77)90098-5
Hess, B., Kutzner, C., Spoel, D. and Lindahl, E. (2008) GROMACS 4: Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. Journal of Chemical Theory and Computation, 4, 435-447. https://doi.org/10.1021/ct700301q
Hornak, V., Abel, R., Okur, A., Strockbine, D., Roitberg, A. and Simmerling, C. (2006) Comparison of Multiple Amber Force Fields and Development of Improved Protein Backbone Parameters. Proteins: Structure Function and Genetics, 65, 712-725. https://doi.org/10.1002/prot.21123
Falkovich, S., Markelov, D., Neelov, I. and Darinskii, A. (2013) Are Structural Properties of Dendrimers Sensitive to the Symmetry of Branching? Computer Simulation of Lysine Dendrimers. Journal of Chemical Physics, 139, Article ID: 064903. https://doi.org/10.1063/1.4817337
Neelov, I., Falkovich, S., Markelov, D., Paci, E., Darinskii, A. and Tenhu, H. (2013) Molecular Dynamics of Lysine Dendrimers. Computer Simulation and NMR. In: Klajnert, B., Peng, L. and Cena, V., Eds., Dendrimers in Biomedical Applications, RSC Publishing, London, 99-114. https://doi.org/10.1039/9781849737296-00099
Neelov, I.M., Janaszewska, A., Klajnert, B., Bryszewska, M., Makova, N., Hicks, D., Pearson, N., Vlasov, G.P., Ilyash, M.Y., Vasilev, D.S., Dubrovskaya, N.L., Zhuravin, I.A., Turner, A.J. and Nalivaeva, N.N. (2013) Molecular Properties of Lysine Dendrimers and Their Interactions with Ab-Peptides and Neuronal Cells. Current Medical Chemistry, 20, 134-143. https://doi.org/10.2174/0929867311302010013
Neelov, I.M., Mistonova, A.A., Khvatov, A.Y. and Bezrodnij, V.V. (2014) Molecular Dynamic Simulation of Peptide Polyelectrolytes. Scientific and Technical Journal of Information Technologies, Mechanics and Optics, 169-175.
Popova, E.V., Shavykin, O.V., Neelov, I.M. and Leemakers, F. (2016) Molecular Dynamics Simulation of Lysine Dendrimer and Semax Peptides Interaction. Scientific and Technical Journal of Information Technologies, Mechanics and Optics, 16, 716-724. https://doi.org/10.17586/2226-1494-2016-16-4-716-724
Markelov, D.A., Falkovich, S.G., Neelov, I.M., Ilyash, M.Y., Matveev, V.V., Lahderanta, E., Ingman, P. and Darinskii, A.A. (2015) Molecular Dynamics Simulation of Spin-Lattice NMR Relaxation in Poly-L-Lysine Dendrimers. Manifestation of the Semiflexibility Effect. Physical Chemistry and Chemical Physics, 17, 3214-3226. https://doi.org/10.1039/C4CP04825C
Ennari, J., Elomaa, M., Neelov, I. and Sundholm, F. (2000) Modelling of Water Free and Water Containing Solid Polyelectrolytes. Polymer, 41, 985-990. https://doi.org/10.1016/S0032-3861(99)00235-9
Ennari, J., Neelov, I. and Sundholm, F. (2000) Comparison of Cell Multipole and Ewald Summation Methods for Solid Polyelectrolyte. Polymer, 41, 2149-2155. https://doi.org/10.1016/S0032-3861(99)00382-1
Ennari, J., Neelov, I. and Sundholm, F. (2000) Molecular Dynamics Simulation of the PEO Sulfonic Acid Anion in Water. Computational and Theoretical Polymer Science, 10, 403-410. https://doi.org/10.1016/S1089-3156(00)00006-4
Ennari, J., Neelov, I. and Sundholm, F. (2000) Molecular Dynamics Simulation of the Structure of PEO Based Solid Polymer Electrolytes. Polymer, 41, 4057-4063. https://doi.org/10.1016/S0032-3861(99)00642-4
Ennari, J., Neelov, I. and Sundholm, F. (2001) Estimation of the Ion Conductivity of a PEO-Based Polyelectrolyte System by Molecular Modeling. Polymer, 42, 8043-8050. https://doi.org/10.1016/S0032-3861(01)00311-1
Ennari, J., Neelov, I. and Sundholm, F. (2004) Modellling of Gas Transport Properties of Polymer Electrolytes Containing Various Amount of Water. Polymer, 45, 4171-4179. https://doi.org/10.1016/j.polymer.2004.03.096
Sadovnichy, V., Tikhonravov, A., Voevodin, V. and Opanasenko, V. (2013) Contemporary High Performance Computing: From Petascale toward Exascale, CRC Press, Boca Raton, 283-307.