1,4-DHP-lipid parameters and rod like micellae

Inta Liepina, Cezary Czaplewski, Adam Liwo, Gunars Duburs

.

DOI: 10.4236/jbpc.2011.24044                

Abstract

The cationic amphiphilic lipid type compound 1,1’-{[3,5-bis(dodecyloxycarbonyl)-4-phenyl-1,4- dihydropyridin-2,6-diyl]dimethylene} bispyridinium dibromide (1,4-DHP lipid) (charge +2), is a gene transfection agent. The electronic structure of 1,4-DHP lipid molecule was investigated by ab initio quantum mechanics, the charges were derived, and the supramolecular structure formed by 1,4-DHP lipid molecules in water was investigated by means of molecular dynamics simulation, f99 force field, version AMBER 8.0. During the molecular dynamics simulations of 10 ns of MD 1,4-DHP lipid formed a worm-like micellae, which was preserved during the time course of 300 ns of MD simulations. Result was confirmed with the electron microscopy showing extended, rod-like structures as one of the 1,4-DHP lipid supramolecular structures, which are expected to be formed at high 1,4-DHP lipid concentrations.

Keywords

Lipid; Gene Transfection; Rod-Like Structure; Worm-Like Micellae; Tubular Micellae; Molecular Dynamics

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Hughes, G.A. (2005) Nanostructure-mediated drug deli- very. Nanomedicine: Nanotechnology, Biology, and Me- dicine, 1, 22-30. doi:10.1016/j.nano.2004.11.009
[2]	Basarkar, A. and Singh, J. (2007) Nanoparticulate sys- tems for polynucleotide delivery. International Journal of Nanomedicine, 2, 353-360.
[3]	Ma, B.-C., Zhang, S.-B., Jiang, H.-M., Zhao, B.-D. and Lv, H.-T. (2007) Lipoplex morphologies and their influences on transfection efficiency in gene delivery. Journal of Controlled Release, 123, 184-194. doi:10.1016/j.jconrel.2007.08.022
[4]	Triggle, D.J. (2006) L-type calcium channels. In: Rampe, D. and Zheng, W., Eds., Voltagegated Ion Channels as Drug Targets. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, 100-122.
[5]	Liepina, I., Blanco, M., Duburs, G. and Liwo, A. (1997) Spatial structure of dihydropyridines and similarity of dihydropyridines with some amino acids. Molecular Engeneering, 7, 401-427. doi:10.1023/A:1008272311650
[6]	Duburs, G., Vigante, B., Plotniece, A., Krauze, A., Sobo- levs, A., Briede, J., Klusa, V. and Velena, A. (2008) Dihy- dropyridine derivatives as bioprotectors. Chemica OGGI/ Chemistry Today, 26, 68-70.
[7]	Hyvonen, Z., Plotniece, A., Reine, I., Chekavichus, B., Duburs, G. and Urtti, A. (2000) Novel cationic amphiphilic 1,4-dihydropyridine derivatives for DNA delivery. Biochimica et Biophysica Acta, 1509, 451-466. doi:10.1016/S0005-2736(00)00327-8
[8]	Hyvonen, Z., Ronkko, S., Toppinen, M.-R., Jaaskelainen, I., Plotniece, A. and Urtti, A. (2004) Dioleoylphosphati Dylethanolamini and PEG-lipid conjugates modify DNA delivery mediated by 1,4-dihydropyridine amphiphiles. Journal of Controlled Release, 99, 177-190. doi:10.1016/j.jconrel.2004.06.019
[9]	SYBYL 8.0, Tripos International, 1699 South Hanley Rd., St. Louis, Missouri, 63144, USA.
[10]	Guest, M.F., Bush, I.J., van Dam, H.J.J., Sherwood, P., Thomas, J.M.H., van Lenthe, J.H., Havenith, R.W.A. and Kendrick, J. (2005) The GAMESS-UK electronic stru- cture package: Algorithms, developments and applica- tions. Molecular Physics, 103, 719-747. doi:10.1080/00268970512331340592
[11]	Zarrabian, S. and Harrison, R.J. (1989) Chemical Physics Letters, 81.
[12]	Saunders, V.R. and van Lenthe, J.H. (1983) Molecular Physics, 48, 923. doi:10.1080/00268978300100661
[13]	Buenker R.J. (1982) Studies in Physical and Theoretical Chemistry, 21, 17.
[14]	Pearlman, D.A., Case, D.A., Caldwell, J.W., Ross, W.S., Cheatham, T.E. III, DeBolt, S., Ferguson, D., Seibel, G. and Kollman, P. (1995) AMBER, a package of computer programs for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to simulate the structural and energetic properties of molecules. Computer Physics Communications, 91, 1-41. doi:10.1016/0010-4655(95)00041-D
[15]	Case, D.A., Cheatham, T., Darden, T., Gohlke, H., Luo, R., Merz, K.M. Jr., Onufriev, A., Simmerling, C., Wang, B. and Woods, R. (2005) The Amber biomolecular simulation programs. Journal of Computational Chemistry, 26, 1668-1688. doi:10.1002/jcc.20290
[16]	Ponder, J.W. and Case, D.A. (2003) Force fields for protein simulations. Advances in Protein Chemistry, 66, 27- 85. doi:10.1016/S0065-3233(03)66002-X
[17]	Humphrey, W., Dalke, A. and Schulten, K. (1996) VMD- Visual Molecular Dynamics. Journal of Molecular Gra- phics, 14, 33-38. doi:10.1016/0263-7855(96)00018-5
[18]	Sayle, R. and Milner-White, E.J. (1995) RasMol: Biomolecular graphics for all. Trends in Biochemical Sciences (TIBS), 20, 374. doi:10.1016/S0968-0004(00)89080-5
[19]	Liepina, I., Czaplewski, C., Ose, V., Danne, R. and Du- burs, G. (2008) 1,4-DHP-lipid forms a tubular micellae. Hansman. H. E., Meinke, Jan H., Mohanty, S., Nadler W. and Zimmermann, O., Eds., Proceedings of NIC Workshop from Computational Biophysics to System Biology, Julich, 19-21 May 2008, 305-307.
[20]	Gajria, S., Neumann, T. and Tirrell, M. (2011) Self-as- sembly and applications of nucleic acid solid-state films. Wiley Interdisciplinary Reviews: Nanomedicine and Na- nobiotechnology. Early View, Article first published online: 2 Jun 2011. doi:10.1002/WNAN.148
[21]	Ma, B., .Zhang, S., Jiang, H., Zhao, B. and Lv, H. (2007) Lipoplex morphologies and their influences on trans- fection efficiency in gene delivery. Journal of Controlled Release, 123, 184-194. doi:10.1016/j.jconrel.2007.08.022
[22]	Ulrich, A.S. (2002) Biophysical aspects of using lipo- somes as delivery vehicles. Bioscience Reports, 22, 129- 150. doi:10.1023/A:1020178304031
[23]	Elouahabi, A. and Ruysschaert, J.-M. (2005) Formation and intracellular trafficking of lipoplexes and polyple- xes. Molecular Therapy, 11, 336-347. doi:10.1016/j.ymthe.2004.12.006