trans-(NH3)(2)Pt(II)-modified deoxyoligonucleotides as potential antisense agents: cross-linking reactions between two 12-mers.
An approach is presented which probes the possible use of trans-[(NH3)(2)PtCl](+)-modified deoxyoligonucleotides in the antisense strategy. It consists of (1) the selective platination of an oligonucleotide containing 11 pyrimidine (T, C) bases as well as a single guanine (G) as a Pt-anchoring group at the 5'-end to give trans-[(NH3)(2)Pt¿5'-d(G(N7)T(2)C(2)T(2)C(2)T(2)C¿Cl](10-) 1 ("antisense strand") and (2) subsequent hybridization with the purine 12-mer 5'-d(GA(2)G(2)A(2)G(2)A(2)G)(11-) ("sense strand"). According to HPLC, three major species 2-4 are formed during reaction (2), all of which are cross-linking adducts between 1 and the sense strand, as confirmed by ESI MS and melting temperature measurements. Only for the major product 3 can a structure be proposed on the basis of 1D and 2D NMR spectra. According to these, G(1) of the antisense strand is cross-linked with G(20) via trans-(NH3)(2)Pt(II). The complementary overhangs of the duplex represent "sticky ends" and are, in principle, capable of associating into multimers of the duplex.
Janik
M B
MB
Fachbereich Chemie, Universität Dortmund Otto-Hahn-Strasse 6, D-44221 Dortmund, Germany.
Lippert
B
B
D002945:Cisplatin / Q000737:chemistry* / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry* / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D020319:Oligodeoxyribonucleotides, Antisense / Q000737:chemistry* / Q000494:pharmacology; D011687:Purines / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects; D013237:Stereoisomerism; D014158:Transcription, Genetic / Q000187:drug effects
D003432:Cross-Linking Reagents; D020319:Oligodeoxyribonucleotides, Antisense; D011687:Purines; D012333:RNA, Messenger; C034697:transplatin; D002945:Cisplatin