第八屆生物物理新知研討會

The 8th Symposium on Recent Advances in Biophysics
I10
Gas-Phase Stabibility of Oligonucleotide Complexes with Drugs            Revealed by Tandem Mass Spectrometry
Hsin-Kai Liao(廖信凱), Yu-Ju Chen*(陳玉如)
Institute of Chemistry, Academia Sinica
To fully characterize the precise nature of damaged DNA on the structural basis is important in understanding the antitumor activity of the ligand on binding to DNA. For short DNA or weakly bounded adduct, no significant difference in the melting temperature (Tm ) of the duplexes can be detected to compare stability between the unmodified duplex and adducted duplex which was modified by covalent binding of small molecules. Tandem mass spectrometry was used to determine the relative stability of double-stranded DNA upon binding of ruthenium complex. Cleavage of the covalent bonds to give rise to the products of neutral base loss, 3’ or 5’ backbone cleavage will compete with dissociation of the two strands, depending on the thermodynamics of the product channels. The extent of fragmentation of the corresponding complex was reduced compared to unbounded duplex, suggesting duplex is stabilized in the gas phase on binding of the ruthenium complex to DNA. However, the two strands are unusually tightly bound upon binding though repulsion between opposite negative phosphate is no longer masked by counter ions in solution. Compared to other spectroscopic methods, binding stoichiometry, specificity and affinity can be determined by mass spectrometry with relatively small amounts of materials.