643755-84-4Relevant articles and documents
Development of a General Aza-Cope Reaction Trigger Applied to Fluorescence Imaging of Formaldehyde in Living Cells
Bruemmer, Kevin J.,Walvoord, Ryan R.,Brewer, Thomas F.,Burgos-Barragan, Guillermo,Wit, Niek,Pontel, Lucas B.,Patel, Ketan J.,Chang, Christopher J.
, p. 5338 - 5350 (2017)
Formaldehyde (FA) is a reactive signaling molecule that is continuously produced through a number of central biological pathways spanning epigenetics to one-carbon metabolism. On the other hand, aberrant, elevated levels of FA are implicated in disease states ranging from asthma to neurodegenerative disorders. In this context, fluorescence-based probes for FA imaging are emerging as potentially powerful chemical tools to help disentangle the complexities of FA homeostasis and its physiological and pathological contributions. Currently available FA indicators require direct modification of the fluorophore backbone through complex synthetic considerations to enable FA detection, often limiting the generalization of designs to other fluorophore classes. To address this challenge, we now present the rational, iterative development of a general reaction-based trigger utilizing 2-aza-Cope reactivity for selective and sensitive detection of FA in living systems. Specifically, we developed a homoallylamine functionality that can undergo a subsequent self-immolative β-elimination, creating a FA-responsive trigger that is capable of masking a phenol on a fluorophore or any other potential chemical scaffold for related imaging and/or therapeutic applications. We demonstrate the utility of this trigger by creating a series of fluorescent probes for FA with excitation and emission wavelengths that span the UV to visible spectral regions through caging of a variety of dye units. In particular, Formaldehyde Probe 573 (FAP573), based on a resorufin scaffold, is the most red-shifted and FA sensitive in this series in terms of signal-to-noise responses and enables identification of alcohol dehydrogenase 5 (ADH5) as an enzyme that regulates FA metabolism in living cells. The results provide a starting point for the broader use of 2-aza-Cope reactivity for probing and manipulating FA biology.
XANTHINE COMPOUND AND USE THEREOF
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, (2018/11/21)
A fluorescent probe for measurement of CYP3A activity, having an excellent CYP molecular species selectivity and detection sensitivity represented is represented by the following formula: In the formula, R1 represents a monovalent group, R2 represents a hydrogen atom or a monovalent group, R3 and R4 each independently represent a hydrogen atom, a halogen atom, an alkyl group or an alkoxy group, R5 represents a monovalent group selected so that the ether bond of the O-benzyl moiety at the 6th position of the compound represented by formula (I) is oxidatively cleavable by the molecular species 3A of the cytochrome P-450, n represents an integer from 1 to 5, and when n is 2 or more, all or a part of the plurality of R5s may be the same as each other or different from each other.
Fluorescence probe for lysophospholipase C/NPP6 activity and a potent NPP6 inhibitor
Kawaguchi, Mitsuyasu,Okabe, Takayoshi,Okudaira, Shinichi,Hanaoka, Kenjiro,Fujikawa, Yuuta,Terai, Takuya,Komatsu, Toru,Kojima, Hirotatsu,Aoki, Junken,Nagano, Tetsuo
, p. 12021 - 12030 (2011/10/02)
Nucleotide pyrophosphatases/phosphodiesterases (NPPs) are ubiquitous membrane-associated or secreted ectoenzymes that have a role in regulating extracellular nucleotide and phospholipid metabolism. Among the members of the NPP family, NPP1 and -3 act on nucleotides such as ATP, while NPP2, -6, and -7 act on phospholipids such as lysophosphatidylcholine and sphingomyelin. NPP6, a recently characterized NPP family member, is a choline-specific glycerophosphodiester phosphodiesterase, but its functions remain to be analyzed, partly due to the lack of highly sensitive activity assay systems and practical inhibitors. Here we report synthesis of novel NPP6 fluorescence probes, TG-mPC and its analogues TG-mPC3C, TG-mPC5C, TG-mPENE, TG-mPEA, TG-mPhos, TG-mPA, TG-mPMe, and TG-mPPr. Among the seven NPPs, only NPP6 hydrolyzed TG-mPC, TG-mPC3C, and TG-mPENE. TG-mPC was hydrolyzed in the cell lysate from NPP6-transfected cells, but not control cells, showing that it is suitable for use in cell-based NPP6 assays. We also examined the usefulness of TG-mPC as a fluorescence imaging probe. We further applied TG-mPC to carry out high-throughput NPP6 inhibitor screening and found several NPP6-selective inhibitors in a library of about 80 000 compounds. Through structure-activity relationship (SAR) analysis, we identified a potent and selective NPP6 inhibitor with an IC50 value of 0.21 μM. Our NPP6-selective fluorescence probe, TG-mPC, and the inhibitor are expected to be useful to elucidate the biological function of NPP6.
