High Efficiency of Transfection Agents Using Bio-Compatable PH Cleavable Linkers

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Published: Mar 30, 2018
Keywords:
Transfection agents, gene therapy, solid phase chemistry, safety-catch linker, pH cleavable linker, liposome, pEGFPLuc plasmid DNA.

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Bordin Chitkul*
Department of Chemistry, Ramkhamhaeng University, Bangkok, Thailand.
Stifun Mittoo
Department of Chemistry, University of Southampton, Southampton, UK.
Mark Bradley
School of Chemistry, University of Edinburgh, UK.

Abstract

Transfection agents were synthesis using solid phase chemistry and utilizing a pH cleavable linker. These compounds are based on 3-Amino-1, 2-propanediol and polyamine conjugate (spermine) to a steroid or bile acids. To optimize the transfection efficiency a series of structure-activity relationship studies were carried out by altering the steroid or fatty acid by systematic variation of the acid chain length. We demonstrate that transfection activity of our compound formulated with DOPE as a co lipid is comparable with commercial available, DC-Chol, transfectam, DOTAP and ESCORTTM respectively. This result suggests our bile acid based cationic lipid is more effective than those commercially available. The most potent compound was N1-(3α,7α-dihydroxy-5β-cholan-24-carbonyl)-1,12-diamino-4,9-diazadecane.


Keywords: Transfection agents, gene therapy, solid phase chemistry, safety-catch linker, pH cleavable linker, liposome, pEGFPLuc plasmid DNA.


Corresponding author: E-mail: b_chitkul@yahoo.com

Article Details

How to Cite
Chitkul*, B., Mittoo, S., & Bradley, M. (2018). High Efficiency of Transfection Agents Using Bio-Compatable PH Cleavable Linkers. CURRENT APPLIED SCIENCE AND TECHNOLOGY, 6(2b), 554–560. retrieved from https://li01.tci-thaijo.org/index.php/cast/article/view/150001
Issue
Vol. 6 No. 2b (2006)
Section
Original Research Articles

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References

[1] Blagbrough, I. S., Carington, S., Geall, A. J., Pham. Sci. 1997, 3, 223-233. Miller, A.D., Angew. Chem. Int. Ed. 1998, 37, 1768-1785.
[2] Crystal R.G., McElvancy, N. G., Rosenfeld, M.A., Chu, C.S., Mastrangeli A.; Hey, J.G., Brody, S.L.; Jaffe, H.A., Eissa, N.T., Danel, C., Nat. Genet., 1994, 8, 42-51. Mulligan, R.C., Science, 1993, 260, 926-931. Crystal, R. G., Science, 1995, 270, 404-410.
[3] Zabner, J., Fasbender, A.D., Moninger, T., Poellinger, K.A., Welsh, M.J., J. Biol. Chem., 1995, 70, 18997-19007.
[4] Escriou, V., Ciolina, C., Lacroix, F., Byk, G., Scherman, D.; Wies, P., Biochim. Biophs.. Acta, 1998, 1368, 276-288.
[5] Byk, G., Wetzer, B., Frederic, M., Dubertret, C., Pitard, B., Jaslin, B., Scherman, D., J. Med. Chem., 2000, 43, 4377-4387.
[6] Chitkul, B., Bradley, M. Optimsing Inhibitors of Trypanothione Reductase Using Solid-phase Chemistry. Bioorg. Med. Cem. Lett., 2000, 10, 2367-2369.
[7] Chitkul, B., Atrash, B., Bradley, M. A New Bio-compatible pH Cleavable Linker for Solid-phase Synthesis of a Squalamine Analogue. Tetrahedron Lett., 2001, 42, 6211-6214.
[8] Blagbrough, I. S., Al-Hadithi, D., Geall, A. J., Tetrahedron, 2000, 56, 3439-3447. Geall, A. J., Tayler, R. J., Earll, M. K., Eaton, M. A. W., Blagbrough, I. S., Bioconjugate Chem., 2000, 11, 314-326.
[9] Machesky, L. Basic RNA and DNA protocol, Harwood, A., Ed., Humana press Inc., Vol. 58, pp 269-271.
[10] Denizot, F., Lang, R., Rapid Colorimetric Assay for Cell Growth and Survival: Modifications to the Tetrazolium Dye Procedue Giving Improved sensitivity and Reliability. J. Immunol. Methods, 1986, 89, 271-277.
[11] Farhood, H., Serbina, N., Huang, L. Biochem. Biophys. Acta 1995, 1235, 289-295; Zelphati, O.; Szoka Jr., F.C. Pharm, Res. 1996, 13, 1367-1372; Friend, D.S.; Papahadjopoulos, D.; Debs, R.J. Biochem. Biophys. Acta 1996, 1278, 41-50.