Book of Abstracts: Albany 2009
June 16-20 2009
© Adenine Press (2008)
Influence of the Location of a Single Stabilizing Chemical Modification on DNA Internal Melting and Strand Dissociation
Usually, with an increase in temperature, long DNAs are melted in the two steps. First, an intramolecular melting starts at a temperature several degrees lower than the melting temperature (Tm). The number of melted base pairs increases with temperature without strand dissociation. Second, strand dissociation arises at a temperature higher than Tm when almost all base pairs are melted. We have considered the influence of stabilizing chemical modifications with and without interstrand crosslinking on both internal melting and strand dissociation. Using experimental data found in literatures and results of our calculations, we have demonstrated that chemical modifications caused by some platinum and ruthenium compounds strongly stabilize the double helix. They increase the free energy of helix-coil transition at sites of their location by more than 10 kcal per mole of modifications. Then we have studied the influence of a single modification of this type on both steps of melting in DNA of 5000 bp. It was found that the influence was strongly dependent on its position along DNA. In general, a single site of stabilization influences both processes. However, a modification located at most unstable AT-rich sites changes differential melting curve without a change in temperature of strand dissociation Td. A modification that locates at the most stable site only slightly influences differential melting curve but strongly increases Td. Both effects are strengthened if interstrand crosslinking occurs besides stabilization at a site of modification.
Dmitri Y. Lando1, 2
1 Institute of Bioorganic Chemistry