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Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

Finding AT-DNA ? Kinetic Recognition of Long Adenine-Thymine Stretches by Metal-Ligand Complexes

Threading of bulky binuclear ruthenium(II) complexes in or out of the base stack in DNA is an extremely slow process that requires a considerable conformational change of the double helix. The rate of intercalation is highly sensitive to the structure and stereochemistry of the metal-ligand coordination and, in particular, to the base sequence around the intercalation site: 2500 times faster with poly(dAdT)2 compared to mixed-sequence DNA for the most selective complex. Studies with oligonucleotides having a central AT-tract of varying length demonstrate that at least one complete helix turn of AT basepairs is necessary for efficient threading, indicating that the transition state involves a stretch of DNA considerably larger than the dimensions of the complex itself. Our results demonstrate that this "kinetic recognition", in which the selection mechanisms go beyond the short-range interactions of a simple lock and key model, can provide a highly sequence-selective DNA interaction.

References and Footnotes
  1. L. M. Wilhelmsson, F. Westerlund, P. Lincoln, B. Nordén. J Am Chem Soc 124, 12092 (2002).
  2. P. Nordell, P. Lincoln. J Am Chem Soc 127, 9670 (2005).
  3. P. Nordell, F. Westerlund, L. M. Wilhelmsson, B. Norden, P. Lincoln. Angew Chem Int Ed In Press (2007).

Pär Nordell*
Fredrik Westerlund
L. Marcus Wilhelmsson
Bengt Nordén
Per Lincoln

Department of Chemical and Biological Engineering/Physical Chemistry
Chalmers University of Technology
SE-412 96 Gothenburg, Sweden

*Phone: +46 31 7723049
Fax: +46 31 7723858
Email: par.nordell@chalmers.se