Tuning the DNA Reactivity of cis-Platinum: Conjugation to a Mismatch-Specific Metallointercalator
A novel bimetallic conjugate combining a rhodium intercalator that selectively binds DNA mismatches and a reactive cis-platinum analogue that targets DNA by coordination has been prepared. The site-selectivity of the bimetallic complex in forming coordination adducts is examined using mismatched and well-matched oligonucleotides of different sequences. The results indicate that through the bifunctional complex, the platinum center can be targeted near mismatched sites. Interestingly, with mismatched, DNA both intrastrand and the less common interstrand cross-linked adducts are formed. The recognition of a DNA mismatch by the bulky Rh intercalator appears to direct the Pt unit, depending upon steric constraints, to react preferentially with mismatched DNA at a site that may or may not be the preferred site of Pt coordination. Thus, the presence of a permanent link to a site-specific intercalator is able to tune the reactivity of the cis-platinum analogue.
© 2004 American Chemical Society. Received May 11, 2004. Publication Date (Web): October 23, 2004. We are grateful to the National Institutes of Health (GM33309) for their financial support. A.P. thanks the French Ministère des Affaires Étrangères for a postdoctoral fellowship (bourse Lavoisier).
Supplemental Material - ja047235lsi20040827_023857.pdf