Bioorganic & Medicinal Chemistry Letters 2008-11-15

A highly sensitive fluorogenic probe for cytochrome P450 activity in live cells.

Melissa M Yatzeck, Luke D Lavis, Tzu-Yuan Chao, Sunil S Chandran, Ronald T Raines

Index: Bioorg. Med. Chem. Lett. 18(22) , 5864-6, (2008)

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Abstract

A derivative of rhodamine 110 has been designed and assessed as a probe for cytochrome P450 activity. This probe is the first to utilize a 'trimethyl lock' that is triggered by cleavage of an ether bond. In vitro, fluorescence was manifested by the CYP1A1 isozyme with k(cat)/K(M)=8.8x10(3)M(-1)s(-1) and K(M)=0.09microM. In cellulo, the probe revealed the induction of cytochrome P450 activity by the carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin, and its repression by the chemoprotectant resveratrol.