A bifunctional molecule as an artificial flavin mononucleotide cyclase and a chemosensor for selective fluorescent detection of flavins.
Flavins, comprising flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD), and riboflavin (RF, vitamin B(2)), play important roles in numerous redox reactions such as those taking place in the electron-transfer chains of mitochondria in all eukaryotes and of plastids in plants. A selective chemosensor for flavins would be useful not only in the investigation of metabolic processes but also in the diagnosis of diseases related to flavins; such a sensor is presently unavailable. Herein, we report the first bifunctional chemosensor (PTZ-DPA) for flavins. PTZ-DPA consists of bis(Zn(2+)-dipicolylamine) and phenothiazine. Bis(Zn(2+)-dipicolylamine) (referred to here as XyDPA) was found to be an excellent catalyst in the conversion of FAD into cyclic FMN (riboflavin 4',5'-cyclic phosphate, cFMN) under physiological conditions, even at pH 7.4 and 27 degrees C, with less than 1 mol % of substrate. Utilizing XyDPA's superior function as an artificial FMN cyclase and phenothiazine as an electron donor able to quench the fluorescence of an isoalloxazine ring, PTZ-DPA enabled selective fluorescent discrimination of flavins (FMN, FAD, and RF): FAD shows ON(+), FMN shows OFF(-), and RF shows NO(0) fluorescence changes upon the addition of PTZ-DPA. With this selective sensing property, PTZ-DPA is applicable to real-time fluorescent monitoring of riboflavin kinase (RF to FMN), alkaline phosphatase (FMN to RF), and FAD synthetase (FMN to FAD).
Rhee
Hyun-Woo
HW
Department of Chemistry, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
Choi
So Jung
SJ
Yoo
Sang Ho
SH
Jang
Yong Oh
YO
Park
Hun Hee
HH
Pinto
Rosa María
RM
Cameselle
José Carlos
JC
Sandoval
Francisco J
FJ
Roje
Sanja
S
Han
Kyungja
K
Chung
Doo Soo
DS
Suh
Junghun
J
Hong
Jong-In
JI
D000588:Amines / Q000737:chemistry; D040761:Biomimetic Materials / Q000737:chemistry* / Q000378:metabolism; D002623:Chemistry Techniques, Analytical / Q000379:methods*; D005486:Flavin Mononucleotide / Q000032:analysis / Q000378:metabolism; D005415:Flavins / Q000032:analysis*; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000032:analysis / Q000737:chemistry; D008163:Luminescent Measurements; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D019761:Phosphorus-Oxygen Lyases / Q000378:metabolism*; D010848:Picolinic Acids / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
C501847:2,2'-dipicolylamine; D000588:Amines; D005415:Flavins; D005456:Fluorescent Dyes; D009942:Organometallic Compounds; D010848:Picolinic Acids; D005486:Flavin Mononucleotide; D019761:Phosphorus-Oxygen Lyases; C111330:FMN cyclase; D015032:Zinc