Influence of initial charge state on fragmentation patterns for noncovalent drug/DNA duplex complexes
| Autor: | Leon P. Oehlers, Karin M. Keller, Jennifer S. Brodbelt, Junmei Zhang |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
chemistry.chemical_classification
Spectrometry Mass Electrospray Ionization Indoles Oligonucleotide Stereochemistry Nogalamycin Daunorubicin Distamycins Netropsin DNA Dissociation (chemistry) chemistry.chemical_compound Crystallography chemistry Oligodeoxyribonucleotides Pharmaceutical Preparations Duplex (building) Covalent bond Non-covalent interactions Benzimidazoles Quadrupole ion trap Spectroscopy |
| Zdroj: | Journal of mass spectrometry : JMS. 40(10) |
| ISSN: | 1076-5174 |
| Popis: | The charge state-dependent dissociation of various DNA duplexes and drug/duplex complexes has been investigated using collisionally activated dissociation (CAD) in a quadrupole ion trap mass spectrometer (QIT-MS). Several non-self-complementary 14-residue oligonucleotides were employed, in addition to an array of known DNA-interactive ligands, including the intercalators daunomycin and nogalamycin, as well as the minor groove binding agents distamycin, netropsin, 4',6-diamidino-2-phenylindole, and Hoechst 33342. In general, the dissociation pathways exhibited by both the duplexes and the drug/duplex complexes were found to be markedly sensitive to initial charge state. Time- and activation voltage-independent duplex strand separation predominated for higher charge states, which was interpreted to be a result of internal Coulombic repulsion or partial unzipping in the interface, while time- and activation voltage-dependent covalent cleavage predominated for lower charge states. The identity of the drug and the sequence of the duplex were both found to affect the competition between different dissociation processes. The dissociation pathways for the lower charge state complexes are probably more reflective of specific drug-DNA interactions because Coulombic and/or conformational effects are less marked for these precursors. |
| Databáze: | OpenAIRE |
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