Poly(l-lysine)-graft-dextran Copolymer Promotes Pyrimidine Motif Triplex DNA Formation at Physiological pH THERMODYNAMIC AND KINETIC STUDIES

作者: Hidetaka Torigoe , Anwarul Ferdous , Hiromitsu Watanabe , Toshihiro Akaike , Atsushi Maruyama

DOI: 10.1074/JBC.274.10.6161

关键词:

摘要: Abstract Extreme instability of pyrimidine motif triplex DNA at physiological pH severely limits its use for artificial control gene expression in vivo. Stabilization the is therefore great importance improving therapeutic potential. To this end, isothermal titration calorimetry interaction analysis system and electrophoretic mobility shift assay have been used to explore thermodynamic kinetic effects our previously reported stabilizer, poly (l-lysine)-graft-dextran (PLL-g-Dex) copolymer, on formation pH. Both analyses clearly indicated that presence PLL-g-Dex binding constant was about 100 times higher than observed without any stabilizer. Of importance, triplex-promoting efficiency copolymer more 20 concentrations spermine, a putative intracellular Kinetic data also demonstrated copolymer-mediated promotion resulted from considerable increase association rate rather decrease dissociation constant. Our results certainly support idea could be key material may eventually lead progress applications antigene strategy

参考文章(43)
Vladimir N. Potaman, Valery N. Soyfer, Triple-helical nucleic acids ,(1995)
Giorgio Manzini, Luigi E. Xodo, Daniela Gasparotto, Franco Quadrifoglio, Gijs A. van der Marel, Jacques H. van Boom, Triple helix formation by oligopurine-oligopyrimidine DNA fragments: Electrophoretic and thermodynamic behavior* Journal of Molecular Biology. ,vol. 213, pp. 833- 843 ,(1990) , 10.1016/S0022-2836(05)80267-0
M. Rougee, B. Faucon, J. L. Mergny, F. Barcelo, C. Giovannangeli, T. Garestier, C. Helene, Kinetics and thermodynamics of triple-helix formation: effects of ionic strength and mismatches. Biochemistry. ,vol. 31, pp. 9269- 9278 ,(1992) , 10.1021/BI00153A021
Paula J. Bates, Harvinder S. Dosanjh, Sanj Kumar, Terence C. Jenkins, Charles A. Laughton, Stephen Neidle, Detection and kinetic studies of triplex formation by oligodeoxynucleotides using real-time biomolecular interaction analysis (BIA) Nucleic Acids Research. ,vol. 23, pp. 3627- 3632 ,(1995) , 10.1093/NAR/23.18.3627
Anwarul Ferdous, Hiromitsu Watanabe, Toshihiro Akaike, Atsushi Maruyama, Comb-type copolymer: Stabilization of triplex DNA and possible application in antigene strategy Journal of Pharmaceutical Sciences. ,vol. 87, pp. 1400- 1405 ,(1998) , 10.1021/JS980066G
D. P. Mascotti, T. M. Lohman, Thermodynamic extent of counterion release upon binding oligolysines to single-stranded nucleic acids. Proceedings of the National Academy of Sciences of the United States of America. ,vol. 87, pp. 3142- 3146 ,(1990) , 10.1073/PNAS.87.8.3142