1071983-26-0Relevant articles and documents
An isophorone-fused near-infrared fluorescent probe with a large Stokes shift for imaging endogenous nitroxyl in living cells and zebrafish
Wei, Chao,Wang, Xiaofen,Li, Xueyan,Jia, Xu,Hao, Xinya,Zhang, Jiangyan,Zhang, Pingzhu,Li, Xiaoliu
, (2020)
Nitroxyl (HNO) plays an important role in multiple physiological and pathological processes, but the detailed generation mechanism of the endogenous HNO still remained to explore and perfect further. There is an urgent need to develop an excellent fluorescent probe for selective recognition and sensitive detection of HNO in biological systems. Near-infrared (NIR) fluorescent probes with a large Stokes shift are an ideal tool for bioimaging applications. Here, we have developed a NIR fluorescent probe with a large Stokes shift, namely, NIR-HNO, to monitor HNO in cells and zebrafish. NIR-HNO consists of an isophorone-fused NIR fluorescence reporter and a diphenylphosphinobenzoyl HNO-responsive unit. Based on an aza-ylide intramolecular ester aminolysis reaction, NIR-HNO showed a rapid selective NIR fluorescent turn-on response for HNO, high sensitivity (detection limit was 39.6 nM), and large Stokes shift (265 nm). The biological imaging results indicate that NIR-HNO is a good candidate for imaging of endogenous HNO in living systems.
A FRET-based ratiometric two-photon fluorescent probe for dual-channel imaging of nitroxyl in living cells and tissues
Zhu, Xiaoyan,Xiong, Mengyi,Liu, Hong-Wen,Mao, Guo-Jiang,Zhou, Liyi,Zhang, Jing,Hu, Xiaoxiao,Zhang, Xiao-Bing,Tan, Weihong
, p. 733 - 736 (2016)
A FRET-based two-photon fluorescent probe, P-Np-Rhod, which exhibited a fast and high selective ratiometric response to nitroxyl, was first proposed. P-Np-Rhod was successfully applied to two-photon dual-channel imaging of nitroxyl in living cells and tis
Comparison of Reductive Ligation-Based Detection Strategies for Nitroxyl (HNO) and S-Nitrosothiols
Miao, Zhengrui,King, S. Bruce
, p. 110 - 114 (2016)
Phosphine-based detection strategies for both nitroxyl (HNO) and S-nitrosothiols (RSNO) were investigated and compared. Phosphorus NMR studies show that azaylides derived from HNO or organic RSNO efficiently participate in subsequent reductive ligation required for fluorescence generation in properly substituted substrates. S-Azaylides derived from biological RSNO containing free amine and carboxylic acid groups primarily yield phosphine oxides suggesting these groups facilitate nonligation pathways such as hydrolysis. The fluorescence response of a phosphine-based fluorophore toward the same RSNO confirms these differences and indicates that these probes selectively react with HNO. Flow cytometry experiments in HeLa cells reinforce the reactivity difference and offer a potential fast screening approach for endogenous HNO sources.
Small Molecule Control of Morpholino Antisense Oligonucleotide Function through Staudinger Reduction
Chen, James K.,Darrah, Kristie,Deiters, Alexander,Lukasak, Bradley,Tsang, Michael,Wesalo, Joshua
supporting information, p. 18665 - 18671 (2021/11/16)
Conditionally activated, caged morpholino antisense agents (cMOs) are tools that enable the temporal and spatial investigation of gene expression, regulation, and function during embryonic development. Cyclic MOs are conformationally gated oligonucleotide analogs that do not block gene expression until they are linearized through the application of an external trigger, such as light or enzyme activity. Here, we describe the first examples of small molecule-responsive cMOs, which undergo rapid and efficient decaging via a Staudinger reduction. This is enabled by a highly flexible linker design that offers opportunities for the installation of chemically activated, self-immolative motifs. We synthesized cyclic cMOs against two distinct, developmentally relevant genes and demonstrated phosphine-triggered knockdown of gene expression in zebrafish embryos. This represents the first report of a small molecule-triggered antisense agent for gene knockdown, adding another bioorthogonal entry to the growing arsenal of gene knockdown tools.
A reductant-resistant and metal-free fluorescent probe for nitroxyl applicable to living cells
Kawai, Kodai,Ieda, Naoya,Aizawa, Kazuyuki,Suzuki, Takayoshi,Miyata, Naoki,Nakagawa, Hidehiko
supporting information, p. 12690 - 12696 (2013/09/23)
Nitroxyl (HNO) is a one-electron reduced and protonated derivative of nitric oxide (NO) and has characteristic biological and pharmacological effects distinct from those of NO. However, studies of its biosynthesis and activities are restricted by the lack of versatile HNO detection methods applicable to living cells. Here, we report the first metal-free and reductant-resistant HNO imaging probe available for use in living cells, P-Rhod. It consists of a rhodol derivative moiety as the fluorophore, linked via an ester moiety to a diphenylphosphinobenzoyl group, which forms an aza-ylide upon reaction with HNO. Intramolecular attack of the aza-ylide on the ester carbonyl group releases a fluorescent rhodol derivative. P-Rhod showed high selectivity for HNO in the presence of various biologically relevant reductants, such as glutathione and ascorbate, in comparison with previous HNO probes. We show that P-Rhod can detect not only HNO enzymatically generated in the horseradish peroxidase-hydroxylamine system in vitro but also intracellular HNO release from Angeli's salt in living cells. These results suggest that P-Rhod is suitable for detection of HNO in living cells.
Mechanism-based triarylphosphine-ester probes for capture of endogenous RSNOs
Seneviratne, Uthpala,Godoy, Luiz C.,Wishnok, John S.,Wogan, Gerald N.,Tannenbaum, Steven R.
, p. 7693 - 7704 (2013/07/11)
Nitrosothiols (RSNOs) have been proposed as important intermediates in nitric oxide (NO?) metabolism, storage, and transport as well as mediators in numerous NO-signaling pathways. RSNO levels are finely regulated, and dysregulation is associated with the etiology of several pathologies. Current methods for RSNO quantification depend on indirect assays that limit their overall specificity and reliability. Recent developments of phosphine-based chemical probes constitute a promising approach for the direct detection of RSNOs. We report here results from a detailed mechanistic and kinetic study for trapping RSNOs by three distinct phosphine probes, including structural identification of novel intermediates and stability studies under physiological conditions. We further show that a triarylphosphine-thiophenyl ester can be used in the absolute quantification of endogenous GSNO in several cancer cell lines, while retaining the elements of the SNO functional group, using an LC-MS-based assay. Finally, we demonstrate that a common product ion (m/z = 309.0), derived from phosphine-RSNO adducts, can be used for the detection of other low-molecular weight nitrosothiols (LMW-RSNOs) in biological samples. Collectively, these findings establish a platform for the phosphine ligation-based, specific and direct detection of RSNOs in biological samples, a powerful tool for expanding the knowledge of the biology and chemistry of NO?-mediated phenomena.
Disulfide formation via sulfenamides
Pan, Jia,Xian, Ming
, p. 352 - 354 (2011/03/17)
A phosphine-mediated one-step disulfide formation from S-nitrosothiols has been developed. This reaction can convert unstable S-nitrosothiols to stable disulfides via sulfenamide intermediates under very mild conditions. It has the potential to be used for the detection of S-nitrosothiols.
Reductive phosphine-mediated ligation of nitroxyl (HNO)
Reisz, Julle A.,Klorlg, Erlka B.,Wright, Marcus W.,King, S. Bruce
supporting information; experimental part, p. 2719 - 2721 (2009/12/03)
Nltroxyl (HNO) demonstrates a unique chemical and biological profile compared to nitric oxide (NO). Phosphorus NMR studies reveal that HNO reacts with triarylphosphines to give the corresponding phosphine oxide and aza-ylide. In the presence of a properly situated electrophilic ester, the aza-ylide undergoes a Staudinger ligation to yield an amide with the nitrogen atom being derived from HNO. These results define new HNO reactivity and provide the basis of new HNO detection methods.
Fast reductive ligation of S-nitrosothiols
Wang, Hua,Xian, Ming
supporting information; experimental part, p. 6598 - 6601 (2009/03/12)
(Chemical Equation Presented) Nitroso knows: A process has been developed which converts unstable S-nitrosothiols into stable sulfenamide analogues (see scheme).Reductive ligation proceeds rapidly in mixed organic solvent/water systems to give high yields. By applying this reaction, an efficient strategy for detecting S-nitrosylation in proteins and other biological systems is envisioned.
