Activity-Based Protein Profiling Methods to Study Bacteria: The Power of Small-Molecule Electrophiles

2018 ◽  
pp. 23-48 ◽  
Author(s):  
Shabnam Sharifzadeh ◽  
Joshua D. Shirley ◽  
Erin E. Carlson
Keyword(s):  
Small Molecule ◽  
Protein Profiling

Chemical Dimerizers in Three-Hybrid Systems for Small Molecule–Target Protein Profiling

2016 ◽  
Vol 11 (8) ◽  
pp. 2075-2090 ◽  
Author(s):  
Dries J. H. De Clercq ◽  
Jan Tavernier ◽  
Sam Lievens ◽  
Serge Van Calenbergh
Keyword(s):  
Hybrid Systems ◽  
Small Molecule ◽  
Protein Profiling ◽  
Target Protein

scholarly journals Discovery of small-molecule enzyme activators by activity-based protein profiling

2020 ◽  
Vol 16 (9) ◽  
pp. 997-1005 ◽  
Author(s):  
Bernard P. Kok ◽  
Srijana Ghimire ◽  
Woojoo Kim ◽  
Shreyosree Chatterjee ◽  
Tyler Johns ◽  
...  
Keyword(s):  
Small Molecule ◽  
Protein Profiling ◽  
Enzyme Activators

scholarly journals A Small-Molecule Activity-Based Probe for Monitoring Ubiquitin C-terminal Hydrolase L1 (UCHL1) Activity in Live Cells and Zebrafish Embryos

2019 ◽  
Author(s):  
Paul P. Geurink ◽  
Raymond Kooij ◽  
Aysegul Sapmaz ◽  
Sijia Liu ◽  
Bo-Tao Xin ◽  
...  
Keyword(s):  
Small Molecule ◽  
Specific Protein ◽  
Cysteine Residue ◽  
Protein Profiling ◽  
Live Cells ◽  
Zebrafish Embryos ◽  
Dependent Manner ◽  
Active Site Cysteine ◽  
Carboxy Terminal

ABSTRACTMany reagents have been emerged to study the function of specific enzymes in vitro. On the other hand, target specific reagents are scarce or need improvement allowing investigations of the function of individual enzymes in a cellular context. We here report the development of a target-selective fluorescent small-molecule activity-based DUB probe that is active in live cells and whole animals. The probe labels active Ubiquitin Carboxy-terminal Hydrolase L1 (UCHL1), also known as neuron-specific protein PGP9.5 (PGP9.5) and parkinson disease 5 (PARK5), a DUB active in neurons that constitutes 1-2% of total brain protein. UCHL1 variants have been linked with the neurodegenerative disorders Parkinson’s and Alzheimer’s disease. In addition, high levels of UCHL1 also correlate often with cancer and especially metastasis. The function of UCHL1 or its role in cancer and neurodegenerative disease is poorly understood and few UCHL1 specific research tools exist. We show that the reagents reported here are specific for UCHL1 over all other DUBs detectable by competitive activity-based protein profiling and by mass spectrometry. Our probe, which contains a cyanimide reactive moiety, binds to the active-site cysteine residue of UCHL1 irreversibly in an activity-dependent manner. Its use is demonstrated by labelling of UCHL1 both in vitro and in cells. We furthermore show that this probe can report UCHL1 activity during the development of zebrafish embryos.

scholarly journals Small-molecule inhibitors of carboxylesterase Notum

2021 ◽  
Author(s):  
Yuguang Zhao ◽  
Sarah Jolly ◽  
Stefano Benvegnu ◽  
E Yvonne Jones ◽  
Paul V Fish
Keyword(s):  
Small Molecule ◽  
Human Disease ◽  
High Throughput Screening ◽  
Small Molecule Inhibitors ◽  
Protein Profiling ◽  
Negative Regulator ◽  
Published Data ◽  
Wnt Proteins ◽  
Fit For Purpose ◽  
Fragment Libraries

Notum has recently been identified as a negative regulator of Wnt signaling through the removal of an essential palmitoleate group from Wnt proteins. There are emerging reports that Notum plays a role in human disease, with published data suggesting that targeting Notum could represent a new therapeutic approach for treating cancer, osteoporosis and neurodegenerative disorders. Complementary hit-finding strategies have been applied with successful approaches that include high-throughput screening, activity-based protein profiling, screening of fragment libraries and virtual screening campaigns. Structural studies are accelerating the discovery of new inhibitors of Notum. Three fit-for-purpose examples are LP-922056, ABC99 and ARUK3001185. The application of these small-molecule inhibitors is helping to further advance an understanding of the role Notum plays in human disease.

scholarly journals Novel Broad-Spectrum Antiviral Inhibitors Targeting Host Factors Essential for Replication of Pathogenic RNA Viruses

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1423
Author(s):  
Marianna Tampere ◽  
Aleksandra Pettke ◽  
Cristiano Salata ◽  
Olov Wallner ◽  
Tobias Koolmeister ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Rna Viruses ◽  
Target Identification ◽  
Protein Profiling ◽  
Screening Assay ◽  
Antiviral Compound ◽  
Antiviral Compounds ◽  
Virus Biology

Recent RNA virus outbreaks such as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ebola virus (EBOV) have caused worldwide health emergencies highlighting the urgent need for new antiviral strategies. Targeting host cell pathways supporting viral replication is an attractive approach for development of antiviral compounds, especially with new, unexplored viruses where knowledge of virus biology is limited. Here, we present a strategy to identify host-targeted small molecule inhibitors using an image-based phenotypic antiviral screening assay followed by extensive target identification efforts revealing altered cellular pathways upon antiviral compound treatment. The newly discovered antiviral compounds showed broad-range antiviral activity against pathogenic RNA viruses such as SARS-CoV-2, EBOV and Crimean-Congo hemorrhagic fever virus (CCHFV). Target identification of the antiviral compounds by thermal protein profiling revealed major effects on proteostasis pathways and disturbance in interactions between cellular HSP70 complex and viral proteins, illustrating the supportive role of HSP70 on many RNA viruses across virus families. Collectively, this strategy identifies new small molecule inhibitors with broad antiviral activity against pathogenic RNA viruses, but also uncovers novel virus biology urgently needed for design of new antiviral therapies.

A privileged ternary blend enabling non-fullerene organic photovoltaics with over 14% efficiency

2020 ◽  
Vol 8 (43) ◽  
pp. 15135-15141
Author(s):  
Jing Yan ◽  
Yuan-Qiu-Qiang Yi ◽  
Jianqi Zhang ◽  
Huanran Feng ◽  
Yanfeng Ma ◽  
...  
Keyword(s):  
Small Molecule ◽  
Organic Photovoltaics ◽  
Power Conversion ◽  
Ternary Blend ◽  
Conversion Efficiencies

Two non-fullerene small molecule acceptors, NT-4F and NT-4Cl, were designed and synthesized. Power conversion efficiencies of 11.44% and 14.55% were achieved for NT-4Cl-based binary and ternary devices, respectively.

The small-molecule antibiotics pipeline: 2014–2018

2019 ◽  
Vol 18 (10) ◽  
pp. 739-739 ◽  
Author(s):  
Cara Lepore ◽  
Lynn Silver ◽  
Ursula Theuretzbacher ◽  
Joe Thomas ◽  
David Visi
Keyword(s):  
Small Molecule

Anisotropic forces in small molecule crystals

1985 ◽  
Vol 82 ◽  
pp. 91-97 ◽  
Author(s):  
H. Bonadeo ◽  
E. Burgos
Keyword(s):  
Small Molecule
Sign in / Sign up

Export Citation Format

Share Document