A highly sensitive fluorogenic probe for cytochrome P450 activity in live cells.
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.
Yatzeck
Melissa M
MM
Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706-1322, USA.
Lavis
Luke D
LD
Chao
Tzu-Yuan
TY
Chandran
Sunil S
SS
Raines
Ronald T
RT
D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis* / Q000378:metabolism; D005456:Fluorescent Dyes; D006801:Humans; D007527:Isoenzymes; D015394:Molecular Structure; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology; D000077185:Resveratrol; D012235:Rhodamines / Q000138:chemical synthesis* / Q000494:pharmacology; D013267:Stilbenes / Q000494:pharmacology; D013329:Structure-Activity Relationship
D005456:Fluorescent Dyes; D007527:Isoenzymes; D000072317:Polychlorinated Dibenzodioxins; D011355:Prodrugs; D012235:Rhodamines; D013267:Stilbenes; C049025:rhodamine 110; D003577:Cytochrome P-450 Enzyme System; D019363:Cytochrome P-450 CYP1A1; D000077185:Resveratrol