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Chemical Biology

A supplement providing a snapshot of the latest developments in chemical biology



A binding agreement


17 March 2006

DNA-binding ligands could be useful for detecting small genetic variations, say researchers in Japan. Norio Teramae and colleagues at Tohoku University, have identified a class of ligands that can recognise a common result of DNA damage called an AP site. 

Detecting DNA damage

An AP site arises when a nucleotide base is lost from DNA, by either spontaneous or enzymatic breakage of the bond connecting it to the DNA backbone. Teramae's group investigated the binding of amiloride, a diuretic containing a pyrazine ring and a guanidinium group, to DNA containing AP sites. The ligand has two groups of hydrogen bond-forming sites capable of binding to both a target nucleotide and an AP site on the opposite strand of the DNA duplex. 

Teramae's team discovered that amiloride displayed reduced fluorescence in the presence of DNA duplexes containing AP sites opposite thymine nucleotides. In contrast there was almost no change in fluorescence response using normal duplexes without AP sites. On further investigation the researchers showed that amiloride strongly and selectively binds the nucleotide thymine with an affinity an order of magnitude greater than for the other three nucleotide bases; adenine, cytosine and guanine. 

"a rational basis for the development of single nucleotide polymorphism detection chemistry based on DNA-binding small molecules"
Amiloride has a striking ability to recognise thymine in duplexes containing an AP site, said Teramae. The results may 'provide a rational basis for the development of single nucleotide polymorphism detection chemistry based on DNA-binding small molecules,' he said.

Kathryn S Lees

References

C Zhao et alChem. Commun., 2006, 1185 (DOI: 10.1039/b516575j)