scholarly journals Label-Free Detection of G Protein–SNARE Interactions and Screening for Small Molecule Modulators

2011 ◽  
Vol 3 (1) ◽  
pp. 69-78 ◽  
Author(s):  
Christopher A. Wells ◽  
Katherine M. Betke ◽  
Craig W. Lindsley ◽  
Heidi E. Hamm
Keyword(s):  
G Protein ◽  
Small Molecule ◽  
Label Free ◽  
Label Free Detection ◽  
Small Molecule Modulators

Label-free detection of small-molecule binding to a GPCR in the membrane environment

2015 ◽  
Vol 1854 (8) ◽  
pp. 979-986 ◽  
Author(s):  
Roland G. Heym ◽  
Wilfried B. Hornberger ◽  
Viktor Lakics ◽  
Georg C. Terstappen
Keyword(s):  
Small Molecule ◽  
Label Free ◽  
Label Free Detection

scholarly journals A Simple Displacement Aptamer Assay on Resistive Pulse Sensor for Small Molecule Detection

2020 ◽  
Author(s):  
Rhushabh Maugi ◽  
bernadette gamble ◽  
david bunka ◽  
Mark Platt
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Label Free ◽  
Resistive Pulse ◽  
Pulse Sensor ◽  
Label Free Detection ◽  
Ssdna Aptamer ◽  
Aptamer Assay ◽  
Small Molecule Detection ◽  
Surface Changes

A universal aptamer-based sensing strategy is proposed using DNA modified nanocarriers and Resistive Pulse Sensing for the rapid and label free detection of small molecules. The surface of a magnetic nanocarrier was first modified with a ssDNA aka linker which is designed to be partially complimentary in sequence to a ssDNA aptamer. The aptamer and linker form a stable dsDNA complex on the nanocarriers surface. Upon the addition of the target molecule, a conformational change takes place where the aptamer preferentially binds to the target over the linker; causing the aptamer to be released into solution. The RPS measures the change in velocity of the nanocarrier as its surface changes from dsDNA to ssDNA, and its velocity is used as a proxy for the concentration of the target. We illustrate the versatility of the assay by demonstrating the detection of the antibiotic Moxifloxacin, and chemotherapeutics Imatinib and Irinotecan.

scholarly journals An aptameric graphene nanosensor for label-free detection of small-molecule biomarkers

2015 ◽  
Vol 71 ◽  
pp. 222-229 ◽  
Author(s):  
Cheng Wang ◽  
Jinho Kim ◽  
Yibo Zhu ◽  
Jaeyoung Yang ◽  
Gwan-Hyoung Lee ◽  
...  
Keyword(s):  
Small Molecule ◽  
Label Free ◽  
Label Free Detection

scholarly journals Mechanism-based sirtuin enzyme activation

2015 ◽  
Author(s):  
Xiangying Guan ◽  
Alok Upadhyay ◽  
Sudipto Munshi ◽  
Raj Chakrabarti
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
False Positives ◽  
Enzyme Activation ◽  
Label Free ◽  
Multiple Substrates ◽  
Dependent Protein ◽  
Biophysical Techniques ◽  
Catalyzed Reactions ◽  
Small Molecule Modulators

AbstractSirtuin enzymes are NAD+-dependent protein deacylases that play a central role in the regulation of healthspan and lifespan in organisms ranging from yeast to mammals. There is intense interest in the activation of the seven mammalian sirtuins (SIRT1-7) in order to extend mammalian healthspan and lifespan. However, there is currently no understanding of how to design sirtuin-activating compounds beyond allosteric activators of SIRT1-catalyzed reactions that are limited to particular substrates. Moreover, across all families of enzymes, only a dozen or so distinct classes of non-natural small molecule activators have been characterized, with only four known modes of activation among them. None of these modes of activation are based on the unique catalytic reaction mechanisms of the target enzymes. Here, we report a general mode of sirtuin activation that is distinct from the known modes of enzyme activation. Based on the conserved mechanism of sirtuin-catalyzed deacylation reactions, we establish biophysical properties of small molecule modulators that can in principle result in enzyme activation for diverse sirtuins and substrates. Building upon this framework, we propose strategies for the identification, characterization and evolution of hits for mechanism-based enzyme activating compounds. We characterize several small molecules reported in the literature to activate sirtuins besides SIRT1, using a variety of biochemical and biophysical techniques including label-free and labeled kinetic and thermodynamic assays with multiple substrates and protocols for the identification of false positives. We provide evidence indicating that several of these small molecules reported in the published literature are false positives, and identify others as hit compounds for the design of compounds that can activate sirtuins through the proposed mechanism-based mode of action.

An ultra-HTS process for the identification of small molecule modulators of orphan G-protein-coupled receptors

2003 ◽  
Vol 8 (17) ◽  
pp. 785-792 ◽  
Author(s):  
Angela Cacace ◽  
Martyn Banks ◽  
Timothy Spicer ◽  
Francesca Civoli ◽  
John Watson
Keyword(s):  
G Protein ◽  
Small Molecule ◽  
G Protein Coupled Receptors ◽  
Small Molecule Modulators ◽  
G Protein Coupled
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