Formation of adenine-N3/guanine-N7 cross-link in the reaction of trans-oriented platinum substrates with dinucleotides.
The reactions of the anticancer complex trans-[PtCl2{(E)-HN=C(OMe)Me}2] (trans-EE) with a series of ribo and deoxyribodinucleotides have been studied by HPLC and 2D [1H, 15N] HMQC NMR spectroscopy and compared with those of the inactive trans isomer of cisplatin, trans-[PtCl2(NH3)2] (trans-DDP). Reactions of trans-EE with r(ApG) and d(ApG) take place through solvolysis of the starting substrate and subsequent formation of trans G-N7/monochloro and G-N7/monoaqua adducts. Slowly, the monofunctional adducts evolve to a bifunctional adduct forming an unprecedented and unexpected A-N3/G-N7 platinum cross-link spanning two trans positions. For stereochemical reasons, trans platinum complexes cannot form N7/N7 cross-links between adjacent purines in di- or polynucleotides. For the reverse sequence r(GpA), no chelate structure was formed even after a two-week reaction. The reaction of trans-DDP with r(ApG) produces many more products than the analogous reaction with trans-EE. One of these products was identified as the A-N3/G-N7 trans-chelate.
Liu
Yangzhong
Y
Department of Chemistry, University of Bergen, Allegt. 41, Norway.
Vinje
Jo
J
Pacifico
Concetta
C
Natile
Giovanni
G
Sletten
Einar
E
D000225:Adenine / Q000737:chemistry* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D002945:Cisplatin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004247:DNA / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D003838:Deoxyadenine Nucleotides / Q000737:chemistry; D003849:Deoxyguanosine / Q000737:chemistry; D006147:Guanine / Q000737:chemistry* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008958:Models, Molecular; D009587:Nitrogen Isotopes; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods
D003432:Cross-Linking Reagents; D003838:Deoxyadenine Nucleotides; D009587:Nitrogen Isotopes; C034697:transplatin; C047743:deoxyadenylyl-(3'-5')-deoxyguanosine; D006147:Guanine; D004247:DNA; D003849:Deoxyguanosine; D000225:Adenine; D002945:Cisplatin