Najia Adnan
MSc Student
Telephone: +61 2
Fax: +61 2
Email:
n.adnan@student.adfa.edu.au
Location:
Field of Study - Biological Chemistry
Supervisor: Assoc. Prof. Grant Collins
Co-Supervisor: Dr Anthony Day
Research Topic - Analysis of DNA Binging of Pixantrone
The reversible DNA-binding of pixantrone and its activated reactive form should be identical, as the binding is due to the intercalculation of the non-reactive planar polycyclic aromatic part of the drug. Consequently, we propose to examine the binding of pixantrone to a range of small segments of DNA (oligonucleotides) by nuclear magnetic resonance (NMR) spectroscopy. In order to compare the DNA-binding of pixantrone to other anthracyclines, initial NMR experiments will utilize a particular well-characterised oligonucleotide. Then, in conjunction with molecular modelling, a detailed picture of the reversible binding will be developed. In the second phase of the research, the reversible binding of pixantrone will be screened against a wide range of oligonucleotides that contain different base sequences and structures (such as base-bulges), using fluorescence intercalator displacement assays. Those sequences or structures that show the strongest pixantrone binding will then be used in subsequent NMR experiments.