Tetrazines-Mediated Bioorthogonal Removal of 3-Isocyanopropyl Groups Enables the Controlled Release of Nitric Oxide In Vivo

2021 ◽  
Author(s):  
Jianbing Wu ◽  
Tao Sun ◽  
Chenxi Yang ◽  
Tian Lv ◽  
Yu-Yang Bi ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Free Radical ◽  
Controlled Release ◽  
Bond Cleavage ◽  
Bioorthogonal Chemistry

Bond cleavage bioorthogonal chemistry has been widely employed to restore or activate proteins or prodrugs. Nitric Oxide (NO), as a free radical molecule, has joined the clinical arena of cancer...

7 Tetrazine-Based Cycloadditions in Click Chemistry

2022 ◽  
Author(s):  
W. Kuba ◽  
M. Wilkovitsch ◽  
J. C. T. Carlson ◽  
H. Mikula
Keyword(s):  
Reaction Mechanisms ◽  
Chemical Biology ◽  
Bond Cleavage ◽  
Therapeutic Strategies ◽  
Complex Environments ◽  
Bioorthogonal Chemistry ◽  
Bioorthogonal Reaction ◽  
Low Concentrations ◽  
Time Critical

AbstractThe spontaneous cycloaddition of tetrazines with a number of different dienophiles has become a powerful tool in chemical biology, in particular for the biocompatible conjugation and modification of (bio)molecules. The exceptional reaction kinetics made these bioorthogonal ligations the methods of choice for time-critical processes at very low concentrations, facilitating controlled molecular transformations in complex environments and even in vivo. The emerging concept of bond-cleavage reactions triggered by tetrazine-based cycloadditions enabled the design of diagnostic and therapeutic strategies. The tetrazine-triggered activation of prodrugs represents the first bioorthogonal reaction performed in humans, marking the beginning of the era of clinical translation of bioorthogonal chemistry. This chapter provides an overview of the synthesis and reactivity of tetrazines, their cycloadditions with various dienophiles, and transformations triggered by these reactions, focusing on reaction mechanisms, kinetics and efficiency, and selected applications.

Free radical biology and medicine: it's a gas, man!

2006 ◽  
Vol 291 (3) ◽  
pp. R491-R511 ◽  
Author(s):  
William A. Pryor ◽  
Kendall N. Houk ◽  
Christopher S. Foote ◽  
Jon M. Fukuto ◽  
Louis J. Ignarro ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Free Radical ◽  
Cell Signaling ◽  
Adaptive Responses ◽  
Adaptive Mechanisms ◽  
Low Levels ◽  
Very High ◽  
Ozone Reactions

We review gases that can affect oxidative stress and that themselves may be radicals. We discuss O2 toxicity, invoking superoxide, hydrogen peroxide, and the hydroxyl radical. We also discuss superoxide dismutase (SOD) and both ground-state, triplet oxygen (3O2), and the more energetic, reactive singlet oxygen (1O2). Nitric oxide (·NO) is a free radical with cell signaling functions. Besides its role as a vasorelaxant, ·NO and related species have other functions. Other endogenously produced gases include carbon monoxide (CO), carbon dioxide (CO2), and hydrogen sulfide (H2S). Like ·NO, these species impact free radical biochemistry. The coordinated regulation of these species suggests that they all are used in cell signaling. Nitric oxide, nitrogen dioxide, and the carbonate radical (CO3·−) react selectively at moderate rates with nonradicals, but react fast with a second radical. These reactions establish “cross talk” between reactive oxygen (ROS) and reactive nitrogen species (RNS). Some of these species can react to produce nitrated proteins and nitrolipids. It has been suggested that ozone is formed in vivo. However, the biomarkers that were used to probe for ozone reactions may be formed by non-ozone-dependent reactions. We discuss this fascinating problem in the section on ozone. Very low levels of ROS or RNS may be mitogenic, but very high levels cause an oxidative stress that can result in growth arrest (transient or permanent), apoptosis, or necrosis. Between these extremes, many of the gasses discussed in this review will induce transient adaptive responses in gene expression that enable cells and tissues to survive. Such adaptive mechanisms are thought to be of evolutionary importance.

scholarly journals Highly specific C–C bond cleavage induced FRET fluorescence for in vivo biological nitric oxide imaging

2017 ◽  
Vol 8 (3) ◽  
pp. 2199-2203 ◽  
Author(s):  
Hua Li ◽  
Deliang Zhang ◽  
Mengna Gao ◽  
Lumei Huang ◽  
Longguang Tang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Real Time ◽  
Bond Cleavage ◽  
Quantitative Imaging ◽  
Dihydropyridine Derivatives

A novel FRET fluorescence “off–on” system based on the highly specific, sensitive and effective C–C bond cleavage of certain dihydropyridine derivatives was reported for real-time quantitative imaging of nitric oxide (NO).

Production of reactive oxygen species after reperfusion in vitro and in vivo: protective effect of nitric oxide

2000 ◽  
Vol 93 (1) ◽  
pp. 99-107 ◽  
Author(s):  
R. Bryan Mason ◽  
Ryszard M. Pluta ◽  
Stuart Walbridge ◽  
David A. Wink ◽  
Edward H. Oldfield ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Free Radical ◽  
Reperfusion Injury ◽  
Oxygen Free Radical ◽  
Content Type ◽  
Free Radical Production ◽  
Radical Production ◽  
Fine Print

Object. Thrombolytic treatments for ischemic stroke can restore circulation, but reperfusion injury, mediated by oxygen free radicals, can limit their utility. The authors hypothesized that, during reperfusion, nitric oxide (NO) provides cytoprotection against oxygen free radical species.Methods. Levels of NO and oxygen free radicals were determined in both reoxygenation in vitro and reperfusion in vivo models using an NO electrochemical probe and high-performance liquid chromatography with the 2,3- and 2,5-dihydroxybenzoic acid trapping method, before and after addition of the NO donor diethanolamine nitric oxide (DEA/NO).Reoxygenation after anoxia produced a twofold increase in NO release by human fetal astrocytes and cerebral endothelial cells (p < 0.005). In both cell lines, there was also a two- to threefold increase in oxygen free radical production (p < 0.005). In human fetal astrocytes and cerebral endothelial cells given a single dose of DEA/NO, free radical production dropped fivefold compared with peak ischemic levels (p < 0.001). In a study in which a rat global cerebral ischemia model was used, NO production in a vehicle-treated group increased 48 ± 16% above baseline levels after reperfusion. After intravenous DEA/NO infusion, NO reached 1.6 times the concentration of the postischemic peak in vehicle-treated animals. In vehicle-treated animals during reperfusion, free radical production increased 4.5-fold over basal levels (p < 0.01). After intravenous DEA/NO infusion, free radical production dropped nearly 10-fold compared with peak levels in vehicle-treated animals (p < 0.006). The infarct volume in the vehicle-treated animals was 111 ± 16.9 mm3; after DEA/NO infusion it was 64.8 ± 23.4 mm3 (p < 0.01).Conclusions. The beneficial effect of early restoration of cerebral circulation after cerebral ischemia is limited by reperfusion injury. These results indicate that NO release and oxygen free radical production increase during reperfusion, and suggest a possible early treatment of reperfusion injury using NO donors.

scholarly journals THE STUDY OF NITRIC OXIDE ACTION IN VIVO ON NA+ , K+ -ÀÒPASE IN RAT AORTA

2009 ◽  
Vol 55 (1) ◽  
pp. 27-35
Author(s):  
O.V. Akopova ◽  
◽  
O.N. Kharlamova ◽  
A.V. Kotsiuruba ◽  
Yu.P. Korkach ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Free Radical ◽  
Atpase Activity ◽  
Rat Aorta ◽  
Radical Reactions ◽  
Hypotensive Action ◽  
No Donor ◽  
Free Radical Reactions ◽  
Stimulation Of

The influence of nitric oxide on Na+,K+-ATPase activity in rat aorta was studied by means of stimulation of endogenous NO synthesis after injections of bacterial lipopolysaccharide (LPS) and pharmacological NO donor nitroglycerine (NG). It was shown that NO action on Na+,K+-ATPase in vivo is dose-de­pendent. Stimulation of the endogenous NO synthesis by LPS as well as the administration of low doses of NG lead to the activation of Na+,K+-ATPase and favor the conclusion that NO-dependent Na+,K+-ATPase stimulation mediates vasodilatory and hypotensive action of nitric oxide. The Na+,K+-ATPase activity in rat aorta depends on the balance between the level of reactive oxygen and nitrogen species (ROS and RNS), forma­tion of NO depots in the tissue of aorta as high- and low mo­lecular weight nitrosothiols, and also on the intensity of free-radical reactions resulting in the generation of hydroperoxide radicals. The results obtained suggest that NOS- and cGMP-dependent pathway takes part in Na+,K+-ATPase activation by LPS and NG, but the enzyme inhibition by nitric oxide in vivo is not cGMP-dependent and is determined by the activation of free-radical reactions and dramatic enhancement of nitrosylation level in rat aorta tissue.

scholarly journals Nitric Oxide and Peroxynitrite in Health and Disease

2007 ◽  
Vol 87 (1) ◽  
pp. 315-424 ◽  
Author(s):  
Pál Pacher ◽  
Joseph S. Beckman ◽  
Lucas Liaudet
Keyword(s):  
Nitric Oxide ◽  
Free Radical ◽  
Mammalian Cells ◽  
Inflammatory Diseases ◽  
Cellular Damage ◽  
Diffusion Controlled ◽  
Wide Range ◽  
Health And Disease ◽  
Therapeutic Tools

The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

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