High-Throughput NMR Techniques for Combinatorial Chemical Library Analysis

ChemInform ◽  
2005 ◽  
Vol 36 (19) ◽  
Author(s):  
Ting Hou ◽  
Daniel Raftery
Keyword(s):  
High Throughput ◽  
Chemical Library ◽  
Nmr Techniques

scholarly journals Identification of a juvenile-hormone signaling inhibitor via high-throughput screening of a chemical library

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Takumi Kayukawa ◽  
Kenjiro Furuta ◽  
Keisuke Nagamine ◽  
Tetsuro Shinoda ◽  
Kiyoaki Yonesu ◽  
...  
Keyword(s):  
Juvenile Hormone ◽  
Cell Line ◽  
Signaling Pathway ◽  
High Throughput ◽  
High Throughput Screening ◽  
Large Scale ◽  
Ex Vivo ◽  
Agricultural Field ◽  
Chemical Library ◽  
Field Development

Abstract Insecticide resistance has recently become a serious problem in the agricultural field. Development of insecticides with new mechanisms of action is essential to overcome this limitation. Juvenile hormone (JH) is an insect-specific hormone that plays key roles in maintaining the larval stage of insects. Hence, JH signaling pathway is considered a suitable target in the development of novel insecticides; however, only a few JH signaling inhibitors (JHSIs) have been reported, and no practical JHSIs have been developed. Here, we established a high-throughput screening (HTS) system for exploration of novel JHSIs using a Bombyx mori cell line (BmN_JF&AR cells) and carried out a large-scale screening in this cell line using a chemical library. The four-step HTS yielded 69 compounds as candidate JHSIs. Topical application of JHSI48 to B. mori larvae caused precocious metamorphosis. In ex vivo culture of the epidermis, JHSI48 suppressed the expression of the Krüppel homolog 1 gene, which is directly activated by JH-liganded receptor. Moreover, JHSI48 caused a parallel rightward shift in the JH response curve, suggesting that JHSI48 possesses a competitive antagonist-like activity. Thus, large-scale HTS using chemical libraries may have applications in development of future insecticides targeting the JH signaling pathway.

Unlocking the Potential of High-Throughput Experimentation for Electrochemistry with a Standardized Microscale Reactor

2021 ◽  
Author(s):  
Jonas Rein ◽  
James R. Annand ◽  
Michael K. Wismer ◽  
Jiantao Fu ◽  
Juno C. Siu ◽  
...  
Keyword(s):  
High Throughput ◽  
Electrochemical Reaction ◽  
Electrochemical Reactor ◽  
Constant Current ◽  
Library Synthesis ◽  
Chemical Library ◽  
Reaction Discovery ◽  
Reaction Optimization ◽  
High Throughput Experimentation ◽  
Broad Array

Organic electrochemistry has emerged as an enabling and sustainable technology in modern organic synthesis. Despite the recent renaissance of electrosynthesis, the broad adoption of electrochemistry in the synthetic community and, especially in industrial settings, has been hindered by the dearth of general, standardized platforms for high-throughput experimentation (HTE). Herein, we disclose the design of the HT<i>e<sup>-</sup></i>Chem, a high-throughput microscale electrochemical reactor that is compatible with existing HTE infrastructure, and enables rapid evaluation of a broad array of electrochemical reaction parameters. Utilizing the HT<i>e<sup>-</sup></i>Chem to accelerate reaction optimization, reaction discovery, and chemical library synthesis is illustrated using a suite of oxidative and reductive transformations under constant current, constant voltage, and electrophotochemical conditions.

scholarly journals Advances in the Use of Microfluidics to Study Crystallization Fundamentals

2019 ◽  
Vol 10 (1) ◽  
pp. 59-83 ◽  
Author(s):  
Nadine Candoni ◽  
Romain Grossier ◽  
Mehdi Lagaize ◽  
Stéphane Veesler
Keyword(s):  
Phase Diagram ◽  
Diffraction Analysis ◽  
High Throughput ◽  
Concentration Measurement ◽  
Ultraviolet Spectroscopy ◽  
X Ray Diffraction ◽  
Chemical Library ◽  
Microfluidic Platform ◽  
X Ray ◽  
Phase Diagram Determination

This review compares droplet-based microfluidic systems used to study crystallization fundamentals in chemistry and biology. An original high-throughput droplet-based microfluidic platform is presented. It uses nanoliter droplets, generates a chemical library, and directly solubilizes powder, thus economizing both material and time. It is compatible with all solvents without the need for surfactant. Its flexibility permits phase diagram determination and crystallization studies (screening and optimizing experiments) and makes it easy to use for nonspecialists in microfluidics. Moreover, it allows concentration measurement via ultraviolet spectroscopy and solid characterization via X-ray diffraction analysis.

scholarly journals Using Weighted Entropy to Rank Chemicals in Quantitative High-Throughput Screening Experiments

2013 ◽  
Vol 19 (3) ◽  
pp. 344-353 ◽  
Author(s):  
Keith R. Shockley
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Nonlinear Models ◽  
Hill Equation ◽  
Parameter Estimates ◽  
Chemical Library ◽  
Data Set ◽  
Screening Experiments ◽  
The Hill ◽  
Weighted Entropy

Quantitative high-throughput screening (qHTS) experiments can simultaneously produce concentration-response profiles for thousands of chemicals. In a typical qHTS study, a large chemical library is subjected to a primary screen to identify candidate hits for secondary screening, validation studies, or prediction modeling. Different algorithms, usually based on the Hill equation logistic model, have been used to classify compounds as active or inactive (or inconclusive). However, observed concentration-response activity relationships may not adequately fit a sigmoidal curve. Furthermore, it is unclear how to prioritize chemicals for follow-up studies given the large uncertainties that often accompany parameter estimates from nonlinear models. Weighted Shannon entropy can address these concerns by ranking compounds according to profile-specific statistics derived from estimates of the probability mass distribution of response at the tested concentration levels. This strategy can be used to rank all tested chemicals in the absence of a prespecified model structure, or the approach can complement existing activity call algorithms by ranking the returned candidate hits. The weighted entropy approach was evaluated here using data simulated from the Hill equation model. The procedure was then applied to a chemical genomics profiling data set interrogating compounds for androgen receptor agonist activity.

scholarly journals A High-Throughput Flow Cytometry Screen Identifies Molecules That Inhibit Hantavirus Cell Entry

2018 ◽  
Vol 23 (7) ◽  
pp. 634-645 ◽  
Author(s):  
Tione Buranda ◽  
Catherine Gineste ◽  
Yang Wu ◽  
Virginie Bondu ◽  
Dominique Perez ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
High Throughput ◽  
Case Fatality ◽  
Hemorrhagic Fever ◽  
Severe Form ◽  
Chemical Library ◽  
Binding Interaction ◽  
Andes Virus ◽  
Bona Fide ◽  
Infection Inhibition

Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), which infects more than 200,000 people worldwide. Sin Nombre virus (SNV) and Andes virus (ANDV) cause the most severe form of HCPS, with case fatality ratios of 30%–40%. There are no specific therapies or vaccines for SNV. Using high-throughput flow cytometry, we screened the Prestwick Chemical Library for small-molecule inhibitors of the binding interaction between UV-inactivated and fluorescently labeled SNVR18 particles, and decay-accelerating factor (DAF) expressed on Tanoue B cells. Eight confirmed hit compounds from the primary screen were investigated further in secondary screens that included infection inhibition, cytotoxicity, and probe interference. Antimycin emerged as a bona fide hit compound that inhibited cellular infection of the major HCPS (SNV)- and HCPS (Hantaan)-causing viruses. Confirming our assay’s ability to detect active compounds, orthogonal testing of the hit compound showed that antimycin binds directly to the virus particle and blocks recapitulation of physiologic integrin activation caused by SNV binding to the integrin PSI domain.

scholarly journals High-throughput sequencing allows the identification of binding molecules isolated from DNA-encoded chemical libraries

2008 ◽  
Vol 105 (46) ◽  
pp. 17670-17675 ◽  
Author(s):  
Luca Mannocci ◽  
Yixin Zhang ◽  
Jörg Scheuermann ◽  
Markus Leimbacher ◽  
Gianluca De Bellis ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
High Throughput ◽  
High Throughput Sequencing ◽  
Organic Molecules ◽  
Relative Quantification ◽  
Dna Encoding ◽  
Chemical Library ◽  
Chemical Libraries ◽  
Matrix Metalloproteinase 3 ◽  
Individual Reaction

DNA encoding facilitates the construction and screening of large chemical libraries. Here, we describe general strategies for the stepwise coupling of coding DNA fragments to nascent organic molecules throughout individual reaction steps as well as the first implementation of high-throughput sequencing for the identification and relative quantification of the library members. The methodology was exemplified in the construction of a DNA-encoded chemical library containing 4,000 compounds and in the discovery of binders to streptavidin, matrix metalloproteinase 3, and polyclonal human IgG.

Chemical library screening for WNK signalling inhibitors using fluorescence correlation spectroscopy

2013 ◽  
Vol 455 (3) ◽  
pp. 339-345 ◽  
Author(s):  
Takayasu Mori ◽  
Eriko Kikuchi ◽  
Yuko Watanabe ◽  
Shinya Fujii ◽  
Mari Ishigami-Yuasa ◽  
...  
Keyword(s):  
High Throughput ◽  
Fluorescence Correlation Spectroscopy ◽  
Correlation Spectroscopy ◽  
Library Screening ◽  
Chemical Library ◽  
Fluorescence Correlation ◽  
Fluorescent Correlation Spectroscopy

To discover WNK–OSR1/SPAK signalling inhibitors, we generated a new high-throughput system using fluorescent correlation spectroscopy capable of screening compounds that disrupt the binding of two molecules. We finally identified two novel and promising compounds for WNK–OSR1/SPAK signalling inhibition.

High-Throughput Screening with HyperCyt® Flow Cytometry to Detect Small Molecule Formylpeptide Receptor Ligands

2005 ◽  
Vol 10 (4) ◽  
pp. 374-382 ◽  
Author(s):  
Susan M. Young ◽  
Cristian Bologa ◽  
Eric R. Prossnitz ◽  
Tudor I. Oprea ◽  
Larry A. Sklar ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
High Throughput ◽  
High Throughput Screening ◽  
Receptor Ligands ◽  
Chemical Library ◽  
Assay Sensitivity ◽  
Compound Libraries ◽  
Analysis System ◽  
G Protein Coupled ◽  
Formylpeptide Receptor

High-throughput flow cytometry (HTFC), enabled by faster automated sample processing, represents a promising high- content approach for compound library screening. HyperCyt® is a recently developed automated HTFC analysis system by which cell samples are rapidly aspirated from microplate wells and delivered to the flow cytometer. The formylpeptide receptor (FPR) family of G protein–coupled receptors contributes to the localization and activation of tissue-damaging leukocytes at sites of chronic inflammation. Here, the authors describe development and application of an HTFC screening approach to detect potential anti-inflammatory compounds that block ligand binding to FPR. Using a homogeneous no-wash assay, samples were routinely processed at 1.5 s/well (~2500 cells analyzed/sample), allowing a 96-well plate to be processed in less than 2.5 min. Assay sensitivity and accuracy were validated by detection of a previously documented active compound with relatively low FPR affinity (sulfinpyrazone, inhibition constant [Ki]=14 μM) from among a collection of 880 compounds in the Prestwick Chemical Library. The HyperCyt® system was therefore demonstrated to be a robust, sensitive, and highly quantitative method with which to screen lead compound libraries in a 96-well format.

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