Cross-linking of a DNA conjugate tethering a cis-bifunctional platinated complex to a target DNA duplex.
Tethering an ethylene diamine linker to the 5' terminus of an oligothymidine sequence provides a ligand for complexation with K2PtCl4. Post-synthetic reaction of the platinum reagent with the diamino oligothymidine generates the diamino dichloro platinum-DNA conjugate that can be used for DNA duplex targeting by oligodeoxyncleotide-mediated triplex formation. Cross-linking between the third strand and the duplex occurs exclusively with the duplex target strand directly involved in triplex formation. No examples of cross-linking to the complementary target strand or cases of cross-linking to both target strands are observed. Most efficient cross-linking occurs when the dinucleotide d(GpG) is present in the target strand and no cross-linking occurs with the corresponding 7-deazaG dinucleotide target. Cross-linking is also observed when dC or dA residues are present in the target strand, or even with a single dG residue, but it is not observed in any cases to dT residues. Triplex formation provides the ability to target specific sequences of double-stranded DNA; conjugates of the type described here offer the potential of delivering a platinum complex to a specific DNA site.
Sharma
Sunil K
SK
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02167, USA.
McLaughlin
Larry W
LW
D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry*; D004247:DNA / Q000138:chemical synthesis / Q000737:chemistry*; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry*
D003432:Cross-Linking Reagents; D009841:Oligonucleotides; D009944:Organoplatinum Compounds; C051802:triplex DNA; D004247:DNA