Journal
JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 98, Issue 10, Pages 1570-1577Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2004.05.001
Keywords
platinum; DNA; triplex; cross-linking; specificity
Funding
- NIGMS NIH HHS [GM 53201] Funding Source: Medline
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Tethering an ethylene diamine linker to the 5' terminus of an oligothymidine sequence provides a site for complexation with (KPtCl4)-Pt-2. Due to the low reactivity of dT toward a platinum source, we chose dT(8) and dT(15) as our initial synthetic targets for platination. 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. The dT(8) sequence is not sufficiently long to facilitate triplex formation and Pt-cross-linking, whereas with a dT(15) sequence 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 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 and the orientational control arising from triplex formation is sufficient to alter the binding preferences of platinum. Conjugates of the type described here offer the potential of delivering a platinum complex to a specific DNA site. (C) 2004 Elsevier Inc. All rights reserved.
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