The rational design of a highly sensitive and selective fluorogenic probe for detecting nitric oxide

2014 ◽  
Vol 50 (49) ◽  
pp. 6475-6478 ◽  
Author(s):  
Sufang Ma ◽  
De-Cai Fang ◽  
Baoming Ning ◽  
Minfeng Li ◽  
Lan He ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Small Molecule ◽  
Rational Design ◽  
Switching Mechanism ◽  
Fluorogenic Probe ◽  
Highly Sensitive

A small-molecule fluorogenic probe for nitric oxide (NO) detection based on a new switching mechanism is developedviaa rational design.

NO, CO and H2S based pharmaceuticals in the mission of vision (eye health): a comprehensive review

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Jan Mohammad Mir ◽  
Ram Charitra Maurya ◽  
Mohd Washid Khan
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Human Physiology ◽  
Hydrogen Sulfide ◽  
The Other ◽  
Normal Functioning ◽  
Comprehensive Review ◽  
Molecular Systems ◽  
Eye Health ◽  
Highly Sensitive

Abstract A set of well defined signaling molecules responsible for normal functioning of human physiology including nitric oxide along with carbon monoxide and hydrogen sulphide are referred as “gasotransmitters”. Due to their involvement in almost every system of a human body, the care of highly sensitive organs using these molecules as drugs represents highly fascinating area of research. In connection with these interesting aspects, the applied aspects of these gaseous molecules in maintaining healthy eye and vision have been targeted in this review. Several examples of eye-droppers including NORMs like latanoprost and nipradiol, CORMs like CORM-3 and CORM-A1, and Hydrogen sulfide releasing system like GYY4137 have been discussed in this context. Therefore the relation of these trio-gasotransmitters with the ophthalmic homeostasis on one hand, and de-infecting role on the other hand has been mainly highlighted. Some molecular systems capable of mimicking gasotransmitter action have also been introduced in connection with the titled theme.

scholarly journals A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

2016 ◽  
Vol 12 ◽  
pp. 125-138 ◽  
Author(s):  
Steven C Zimmerman
Keyword(s):  
Small Molecules ◽  
Supramolecular Chemistry ◽  
Myotonic Dystrophy ◽  
Small Molecule ◽  
Early Life ◽  
Rational Design ◽  
Early Experience ◽  
Therapeutic Agents ◽  
Early Career ◽  
Molecular Tweezers

This review summarizes part of the author’s research in the area of supramolecular chemistry, beginning with his early life influences and early career efforts in molecular recognition, especially molecular tweezers. Although designed to complex DNA, these hosts proved more applicable to the field of host–guest chemistry. This early experience and interest in intercalation ultimately led to the current efforts to develop small molecule therapeutic agents for myotonic dystrophy using a rational design approach that heavily relies on principles of supramolecular chemistry. How this work was influenced by that of others in the field and the evolution of each area of research is highlighted with selected examples.

scholarly journals Catechol-Containing Compounds are a Broad Class of Protein Aggregation Inhibitors: Redox State is a Key Determinant of the Inhibitory Activities

2020 ◽  
Author(s):  
Paul Velander ◽  
Ling Wu ◽  
Sherry B. Hildreth ◽  
Nancy J. Vogelaar ◽  
Biswarup Mukhopadhyay ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Small Molecule ◽  
Rational Design ◽  
Redox State ◽  
Broad Class ◽  
Intrinsically Disordered ◽  
Amyloidogenic Proteins ◽  
Key Factor ◽  
Inhibitory Activities ◽  
Screening Platform

Abstract Background: A range of neurodegenerative and related aging diseases, such as Alzheimer’s disease, Parkinson’s disease, and type 2 diabetes, are linked to toxic protein aggregation. Yet the mechanisms of protein aggregation inhibition by small molecule inhibitors remain poorly understood, in part because most protein targets of aggregation assembly are partially unfolded or intrinsically disordered, which hinders detailed structural characterization of protein-inhibitor complexes and structural-based mechanistic elucidation. Methods: Herein we employed a small molecule screening approach to identify inhibitors against three prototype amyloidogenic proteins in neurodegeneration and related proteinopathies: amylin, Ab and tau. We further systematically investigated selected class of inhibitors under aerobic and anaerobic conditions to uncover a key determinant of the inhibitory activities.Results: One remarkable class of inhibitors identified from all three parallel screenings against different amyloidogenic proteins was catechol-containing compounds and redox-related quinones/anthraquinones. Further mechanistic studies determined that the redox state of the broad class of catechol-containing compounds is a key determinant of the amyloid inhibitor activities. Conclusion: Our small molecule library screening platform was able to identify a broad class of amyloid inhibitors. Redox was found to be a key factor not only regulating the inhibitory activities but also involving the mechanism of inhibition. The molecular insights we gained not only explain why a large number of catechol-containing natural compounds, often enriched in healthy diet, have anti-neurodegeneration and anti-aging activities, but also could guide the rational design of therapeutic or nutraceutical strategies to target a broad range of neurodegenerative and related aging diseases.

Rational Design of Selective Small-Molecule Inhibitors for β-Catenin/B-Cell Lymphoma 9 Protein–Protein Interactions

2015 ◽  
Vol 137 (38) ◽  
pp. 12249-12260 ◽  
Author(s):  
Logan R. Hoggard ◽  
Yongqiang Zhang ◽  
Min Zhang ◽  
Vanja Panic ◽  
John A. Wisniewski ◽  
...  
Keyword(s):  
B Cell ◽  
Small Molecule ◽  
Protein Interactions ◽  
Rational Design ◽  
Small Molecule Inhibitors ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Protein Protein Interactions ◽  
Catenin B
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