Triplex mediated delivery of a platinum complex to a specific DNA target site.
Triplex mediated delivery of a platinum complex to a specific DNA target site.
复制标题
DOI：
10.1016/j.jinorgbio.2004.05.001
复制
发表时间：
2004-10
影响因子：
3.9
通讯作者：
Sunil K. Sharma;L. McLaughlin
中科院分区：
文献类型：
--
作者：
Sunil K. Sharma;L. McLaughlin
Tethering an ethylene diamine linker to the 5′terminus of an oligothymidine sequence provides a site for complexation with K2PtCl4. Due to the low reactivity of dT toward a platinum source, we chose dT8and dT15as 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 dT8sequence is not sufficiently long to facilitate triplex formation and Pt-cross-linking, whereas with a dT15sequence 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.
