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Predicting drug response
27 August 2010
Scientists in China have developed a probe that could be used to test how well a patient will respond to certain drug treatments.
The new probe measures the activity of N-acetyltransferase 2 (NAT2), an enzyme that metabolises drugs and other toxins containing aryl amines and hydrazines. The activity of NAT2 differs between individuals, which affects how well a drug will work, and dysfunction of the enzyme has been linked to breast cancer, Parkinson's and other diseases. A simple measure of NAT2 activity could help ensure patients are given drugs that they can metabolise effectively with minimal side effects.
Xuhong Qian and colleagues at the East China University of Science and Technology in Shanghai found that the fluorescent molecule amonafide is metabolised specifically by NAT2. The enzyme acetylates the probe molecule, shifting its flourescence wavelength. Hence, this fluorescence change correlates to NAT2 activity. Current methods for predicting patient response to certain drugs require complex genetic analysis, but this probe could provide a simple and sensitive test.
Acetylation by NAT2 changes the fluorescence wavelength of amonafide
AP de Silva, an expert in fluorescent sensors at Queen's University Belfast, UK, admires the team's use of fluorescence in two colours to monitor an intracellular enzyme. He adds 'this work is likely to attract favourable attention.'
'The probe has significant potential applications in personal medicine,' Qian says. 'We also hope that it can be used to study the mechanism of different kinds of diseases related to NAT2.' The team now intends to design probes for other important enzymes.
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Link to journal article
Selective and sensitive detection and quantification of arylamine N-acetyltransferase 2 by a ratiometric fluorescence probe
Lei Cui, Ye Zhong, Weiping Zhu, Yufang Xu and Xuhong Qian, Chem. Commun., 2010, 46, 7121
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