Researchers from the University of New England have developed a way of targeting molecules to DNA, which could be useful in the design of more effective anti-cancer chemotherapy drugs.
Professor Steve Glover from the School of Science and Technology says a large number of drugs are designed to target DNA.
“Using a class of DNA damaging agents called N-acyloxy-N-alkoxy amides (NAA’s) we have shown that a simple molecule, naphthalene, when attached to NAA’s will significantly enhance their reaction with bacterial DNA.”
He says this work provides the first compelling evidence for naphthalene intercalation, a process whereby the flat naphthalene group slides in between the base pairs or rungs of the DNA ladder.
“For drugs to be able to interact with the contents of cells, they must first pass through a barrier cell membrane that is designed to protect the cell from chemicals. However, there is a limit to the size of molecules that can pass through this membrane,” said Professor Glover.
The membrane will usually trap larger organic molecules. This reduces their efficiency, since not enough molecules reach the DNA target inside the cell.
“What makes our finding useful is that naphthalene is a small group, and its incorporation into NAA’s still enables them to penetrate the cell membrane. However, once inside the cell the activity of NAA’s is enhanced by their attraction to DNA through the intercalation process. This enhancement in activity is not trivial. For an NAA without an attached naphthalene group to possess a similar level of reactivity it would certainly be too large to pass through the cell membrane.
So by incorporating the naphthalene group it could provide an effective means of targeting molecules to DNA.
The research was recently featured on the front cover of the Royal Society of Chemistry’s Journal of Organic and Biomolecular Chemistry.