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DNA hydrolysis by tris-triazacyclononanes metal complexes
Journal
of Inorganic biochemistry 96 (‘2003)
hydrolysis by Tris-triazacycl ~hie~-~~un~ Cheng Department of Chemistry, Tamkang Universi@, Tahan Yan-AshenHuang, department of Chemistry, Tamkang University, Taiwan ~in~-~h~n Liu, department of Chemistry, National Taiwan University, Taiwan A ~~~ro~y§is,metal The use of multi-nuclear metal complexes is getting interests in mimicking enzyme functions. la as a ~ucleo~hile ts ions are known to act as a Lewis acid to stabilize the transition state and to form a metal-hydro attack the phosphodiester bonds. The synthetic bimetallic complexes containing both factors were found to ~~~a~~ethe cleavage of double-stranded DNA at 37°C and pH 8. Recently, trinuclear copper complex shows t third metal ion as with a DNA junction between single- and double-stranded regions. The use of double Lewis a a n~~Ieo~hile may improve the reactivity and selectivity of multi-nuclear metal complexes in ovel coordinate ligand was designed and synthesizedto contain three 1,4,7-triaza~y~Iononanes(TA osition. The formation of metal complexes with different metal ions such as Zr?‘, Co’+, Cu2+,I, aracterized by electronic absorption and ESI-mass spectroscopy. The hydrolysis product analyzed by discussed. The ability of DNA hydrolysis and the sequence selectivity with different metal complexes were studied by agarose gel and polyacrylamide gel electrophoresis in different buffers, p
tudies on new homonuclear complexes with w The University of Sydney,Australia Fazlul Huq, The University ofsydney, Australia Philip Beale, Sydney Cancer Centre - CSAHS, Australia Currently platinum compounds with structures different from that of cisplatin are being ~o~sider~~with tP1eidea that they ave a different spectrum of activity and might not develo cross-resistance to ~is~lat~~~ BBR3464 which is characterized by activity in human tumour (e.g ovarian) resistant to cisplatin and alk~~a~i~~agents, a high activity in a broad spectrum of tumours commonly insensitive to chemotherapeutic interven second stage of ciinical trial. BBR3464 has three trans-platinum units connected together by alkyl latinum units bind covalently with nucleobases in A, the central ~lati~~rn unit is believed to undergo interactions including electrostatic interaction an We hypothesized that while the replacement of the central platinu er suitable metal units or ~~ati~~~ b~n~~~ to one or more ~lanar~i~es instead of ammonia ligands would not markedly alter the covalent i~t~ra~~i~~sof the terminal units with DNA, it would have a subtle effect on the non-covalent interactions of the central un result in anticancer active compounds with a different spectrum o and h~t~ro~~~learmetal complexes with multiple metal centres NA. Starting materials, transplatin and its analogue, have been prep made to synthesis a number of compounds of the form: [trans-Cl -tra~s-~l(~~*~t~X~, where M stands for Pt2+, CU*+ and Co3+, L stan s for a carbon chain and X stands for a singly charged negative ion. The complexes are of synthesis and purified by repeated dissolution and crystallization. Interaction with ~le~tr~~horesis,FIPLC, AAS, UV-visible spectrophotometry and restriction enzyme ~~s~la~i~-responsive and cisplatin-resistant cancer cell-lines is dete
of Inorganic biochemistry 96 (‘2003)
hydrolysis by Tris-triazacycl ~hie~-~~un~ Cheng Department of Chemistry, Tamkang Universi@, Tahan Yan-AshenHuang, department of Chemistry, Tamkang University, Taiwan ~in~-~h~n Liu, department of Chemistry, National Taiwan University, Taiwan A ~~~ro~y§is,metal The use of multi-nuclear metal complexes is getting interests in mimicking enzyme functions. la as a ~ucleo~hile ts ions are known to act as a Lewis acid to stabilize the transition state and to form a metal-hydro attack the phosphodiester bonds. The synthetic bimetallic complexes containing both factors were found to ~~~a~~ethe cleavage of double-stranded DNA at 37°C and pH 8. Recently, trinuclear copper complex shows t third metal ion as with a DNA junction between single- and double-stranded regions. The use of double Lewis a a n~~Ieo~hile may improve the reactivity and selectivity of multi-nuclear metal complexes in ovel coordinate ligand was designed and synthesizedto contain three 1,4,7-triaza~y~Iononanes(TA osition. The formation of metal complexes with different metal ions such as Zr?‘, Co’+, Cu2+,I, aracterized by electronic absorption and ESI-mass spectroscopy. The hydrolysis product analyzed by discussed. The ability of DNA hydrolysis and the sequence selectivity with different metal complexes were studied by agarose gel and polyacrylamide gel electrophoresis in different buffers, p
tudies on new homonuclear complexes with w The University of Sydney,Australia Fazlul Huq, The University ofsydney, Australia Philip Beale, Sydney Cancer Centre - CSAHS, Australia Currently platinum compounds with structures different from that of cisplatin are being ~o~sider~~with tP1eidea that they ave a different spectrum of activity and might not develo cross-resistance to ~is~lat~~~ BBR3464 which is characterized by activity in human tumour (e.g ovarian) resistant to cisplatin and alk~~a~i~~agents, a high activity in a broad spectrum of tumours commonly insensitive to chemotherapeutic interven second stage of ciinical trial. BBR3464 has three trans-platinum units connected together by alkyl latinum units bind covalently with nucleobases in A, the central ~lati~~rn unit is believed to undergo interactions including electrostatic interaction an We hypothesized that while the replacement of the central platinu er suitable metal units or ~~ati~~~ b~n~~~ to one or more ~lanar~i~es instead of ammonia ligands would not markedly alter the covalent i~t~ra~~i~~sof the terminal units with DNA, it would have a subtle effect on the non-covalent interactions of the central un result in anticancer active compounds with a different spectrum o and h~t~ro~~~learmetal complexes with multiple metal centres NA. Starting materials, transplatin and its analogue, have been prep made to synthesis a number of compounds of the form: [trans-Cl -tra~s-~l(~~*~t~X~, where M stands for Pt2+, CU*+ and Co3+, L stan s for a carbon chain and X stands for a singly charged negative ion. The complexes are of synthesis and purified by repeated dissolution and crystallization. Interaction with ~le~tr~~horesis,FIPLC, AAS, UV-visible spectrophotometry and restriction enzyme ~~s~la~i~-responsive and cisplatin-resistant cancer cell-lines is dete