A supplement providing a snapshot of the latest developments in chemical biology
Ringing the changes to combat cancer
21 February 2006
A new class of targeted anticancer drugs could soon be developed thanks to researchers from France who have prepared cyclic macromolecules that selectively bind four stranded DNA structures.
The macrocycles prepared are a radical departure from the flat aromatic compounds typically used for DNA quadruplex binding. The macrocycles consist of an aminoglycoside tethered at each end to an aromatic platform to form a ring. Teulade-Fichou wanted to combine the nucleic acid-binding properties of aminoglycosides with the ability of aromatic molecules to insert into the DNA strand.
The cyclic nature of the molecules causes the aminoglycoside components to be curved like a dome, which binds within the loops of the folded quadruplex DNA structure. The dome-like shape also results in the macrocycle having a low affinity for normal linear DNA.
Having shown that the new macrocycles can bind pre-formed quadruplexes, the next step will be to test their ability to induce quadruplexes to form from single strand DNA. The new molecules are 'attractive structural scaffolds for further developments aimed at the discovery of new and more selective anticancer agents,' said Teulade-Fichou.
James Mitchell Crow