Monofunctionally trans-diammine platinum(II)-modified peptide nucleic acid oligomers: a new generation of potential antisense drugs.
A solid-phase approach is described that provides facile access to monofunctionally trans-PtII-modified PNA oligomers of arbitrary sequence for potential use both in antigene and antisense strategies. The approach includes the synthesis of a platinated building block 1 and its subsequent incorporation into three different PNA oligomers 5-7 by solid-phase synthesis. In a model cross-linking reaction one of the latter is found to recognize sequence-specifically a target oligonucleotide 8 and to cross-link to it. The resulting structure is the trans-PtII-cross-linked PNA/DNA duplex 9 as revealed by mass spectrometry in combination with a Maxam-Gilbert sequencing experiment.
Schmidt
Kathrin S
KS
Fachbereich Chemie, Universität Dortmund Otto-Hahn-Strasse 6, 44227 Dortmund, Germany.
Boudvillain
Marc
M
Schwartz
Annie
A
van der Marel
Gijs A
GA
van Boom
Jacques H
JH
Reedijk
Jan
J
Lippert
Bernhard
B
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002945:Cisplatin / Q000737:chemistry*; D003432:Cross-Linking Reagents; D004247:DNA / Q000737:chemistry; D016373:DNA, Antisense / Q000138:chemical synthesis / Q000737:chemistry*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D009696:Nucleic Acids / Q000138:chemical synthesis / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D012333:RNA, Messenger / Q000096:biosynthesis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D016373:DNA, Antisense; D007202:Indicators and Reagents; D009696:Nucleic Acids; D010455:Peptides; D012333:RNA, Messenger; D004247:DNA; D002945:Cisplatin