scholarly journals A Ligand-Directed Approach to Activity-Based Sensing: Developing Palladacycle Fluorescent Probes that Enable Endogenous Carbon Monoxide Detection

Author(s):  
Johannes Morstein ◽  
Denis Höfler ◽  
Kohei Ueno ◽  
Jonah Jurss ◽  
Ryan Walvoord ◽  
...  

Carbon monoxide (CO) is an emerging gasotransmitter and reactive carbon species with broad anti-inflammatory, cytoprotective, and neurotransmitter functions along with therapeutic potential for the treatment of cardiovascular diseases. The study of CO chemistry in biology and medicine relative to other prominent gasotransmitters such as NO and H2S remains challenging, in large part due to limitations in available tools for the direct visualization of this transient and freely diffusing small molecule in complex living systems. Here we report a ligand-directed activity-based sensing (ABS) approach to CO detection through palladium-mediated carbonylation chemistry. Specifically, the design and synthesis of a series of ABS probes with systematic alterations in the palladium-ligand environment (e.g., sp3-S, sp3-N, sp2-N) establish structureactivity relationships for palladacycles to confer selective reactivity with CO under physiological conditions. These fundamental studies led to the development of an optimized probe, termed Carbon Monoxide Probe-3 Ester Pyridine (COP3E-Py), which enables imaging of CO release in live cell and brain settings, including monitoring of endogenous CO production that triggers presynaptic dopamine release in fly brains. This work provides a unique tool for studying CO in living systems and establishes the utility of a synthetic methods approach to activity-based sensing using principles of organometallic chemistry

2020 ◽  
Author(s):  
Johannes Morstein ◽  
Denis Höfler ◽  
Kohei Ueno ◽  
Jonah Jurss ◽  
Ryan Walvoord ◽  
...  

Carbon monoxide (CO) is an emerging gasotransmitter and reactive carbon species with broad anti-inflammatory, cytoprotective, and neurotransmitter functions along with therapeutic potential for the treatment of cardiovascular diseases. The study of CO chemistry in biology and medicine relative to other prominent gasotransmitters such as NO and H2S remains challenging, in large part due to limitations in available tools for the direct visualization of this transient and freely diffusing small molecule in complex living systems. Here we report a ligand-directed activity-based sensing (ABS) approach to CO detection through palladium-mediated carbonylation chemistry. Specifically, the design and synthesis of a series of ABS probes with systematic alterations in the palladium-ligand environment (e.g., sp3-S, sp3-N, sp2-N) establish structureactivity relationships for palladacycles to confer selective reactivity with CO under physiological conditions. These fundamental studies led to the development of an optimized probe, termed Carbon Monoxide Probe-3 Ester Pyridine (COP3E-Py), which enables imaging of CO release in live cell and brain settings, including monitoring of endogenous CO production that triggers presynaptic dopamine release in fly brains. This work provides a unique tool for studying CO in living systems and establishes the utility of a synthetic methods approach to activity-based sensing using principles of organometallic chemistry


2018 ◽  
Vol 24 (20) ◽  
pp. 2283-2302 ◽  
Author(s):  
Vivian B. Neis ◽  
Priscila B. Rosa ◽  
Morgana Moretti ◽  
Ana Lucia S. Rodrigues

Heme oxygenase (HO) family catalyzes the conversion of heme into free iron, carbon monoxide and biliverdin. It possesses two well-characterized isoforms: HO-1 and HO-2. Under brain physiological conditions, the expression of HO-2 is constitutive, abundant and ubiquitous, whereas HO-1 mRNA and protein are restricted to small populations of neurons and neuroglia. HO-1 is an inducible enzyme that has been shown to participate as an essential defensive mechanism for neurons exposed to oxidant challenges, being related to antioxidant defenses in certain neuropathological conditions. Considering that neurodegenerative diseases (Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Multiple Sclerosis (MS)) and neuropsychiatric disorders (depression, anxiety, Bipolar Disorder (BD) and schizophrenia) are associated with increased inflammatory markers, impaired redox homeostasis and oxidative stress, conditions that may be associated with alterations in HO-levels/activity, the purpose of this review is to present evidence on the possible role of HO-1 in these Central Nervous System (CNS) diseases. In addition, the possible therapeutic potential of targeting brain HO-1 is explored in this review.


2011 ◽  
Vol 37 (6) ◽  
pp. 497-499 ◽  
Author(s):  
A. S. Golovin ◽  
A. A. Petukhov ◽  
S. S. Kizhaev ◽  
Yu. P. Yakovlev

2017 ◽  
Vol 7 (6) ◽  
pp. 17
Author(s):  
Wamik Azmi ◽  
Shikha Chauhan ◽  
Manisha Gautam

Collagen is the most widely distributed class of proteins in the human body. Monomers of collagen are constantly being synthesized and degraded throughout the development of a healthy individual to adulthood. The collagenase subfamily found in human matrix (metalloproteinases), are capable of hydrolyzing native collagen under physiological conditions. Collagenases are produced by specific cells involved in repairs and remodelling processes and plays important role in connective tissue metabolism. Present article focus on the major sources, properties and therapeutic aspects of microbial collagenases in their relation with various diseases and its applications in medical and food industry. Collagenolytic enzymes are highly specific for collagen and have been the focus of much practical interest with respect to cosmetic, medical and food based applications. The most common uses of these enzymes appear to be in medicine as they have been used to treat burns and ulcers, to eliminate scar tissue and play an important role in the successful transplantation of specific organs.


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