Emissive Synthetic Cofactors: Enzymatic Interconversions of tzA Analogues of ATP, NAD+, NADH, NADP+, and NADPH

A series of enzymatic transformations, which generate visibly emissive isofunctional cofactors based on an isothiazolo[4,3‐d]pyrimidine analogue of adenosine (tzA), was developed. Nicotinamide adenylyl transferase condenses nicotinamide mononucleotide and tzATP to yield NtzAD+, which can be enzymati...

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Published inAngewandte Chemie International Edition Vol. 57; no. 4; pp. 1087 - 1090
Main Authors Hallé, François, Fin, Andrea, Rovira, Alexander R., Tor, Yitzhak
Format Journal Article
LanguageEnglish
Published Weinheim Wiley Subscription Services, Inc 22.01.2018
EditionInternational ed. in English
Subjects
Adenosine
ATP
Cofactors
Fluorescence
Fluorescence spectroscopy
Glucose 6 phosphate dehydrogenase
Glucosephosphate dehydrogenase
Glutathione
Glutathione reductase
kinases
NAD
NADH
NADP
NADPH
Nicotinamide
Nicotinamide adenine dinucleotide
nucleotides
Phosphates
Reoxidation
Transformations
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Summary:A series of enzymatic transformations, which generate visibly emissive isofunctional cofactors based on an isothiazolo[4,3‐d]pyrimidine analogue of adenosine (tzA), was developed. Nicotinamide adenylyl transferase condenses nicotinamide mononucleotide and tzATP to yield NtzAD+, which can be enzymatically phosphorylated by NAD+ kinase and ATP or tzATP to the corresponding NtzADP+. The latter can be engaged in NADP‐specific coupled enzymatic transformations involving conversion to NtzADPH by glucose‐6‐phosphate dehydrogenase and reoxidation to NtzADP+ by glutathione reductase. The NtzADP+/NtzADPH cycle can be monitored in real time by fluorescence spectroscopy. Relatives in the spotlight: A series of enzymatic transformations generate visibly emissive isofunctional cofactors based on an isothiazolo[4,3‐d]pyrimidine analogue of adenosine (tzA, see figure). These synthetic cofactors may find utility as tools for monitoring redox reactions in vitro or potentially in living systems.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201711935