scholarly journals Label-Free High-Throughput Leukemia Detection by Holographic Microscopy

2018 ◽  
Vol 5 (12) ◽  
pp. 1800761 ◽  
Author(s):  
Matthias Ugele ◽  
Markus Weniger ◽  
Manfred Stanzel ◽  
Michael Bassler ◽  
Stefan W. Krause ◽  
...  
Lab on a Chip ◽  
2018 ◽  
Vol 18 (12) ◽  
pp. 1704-1712 ◽  
Author(s):  
Matthias Ugele ◽  
Markus Weniger ◽  
Maria Leidenberger ◽  
Yiwei Huang ◽  
Michael Bassler ◽  
...  

Label-free, high-throughput holographic microscopy enables malaria detection at the ring stage and distinction ofP. falciparumlife cycle stages.


2021 ◽  
Vol 22 (9) ◽  
pp. 4417
Author(s):  
Lester J Lambert ◽  
Stefan Grotegut ◽  
Maria Celeridad ◽  
Palak Gosalia ◽  
Laurent JS De Backer ◽  
...  

Many human diseases are the result of abnormal expression or activation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Not surprisingly, more than 30 tyrosine kinase inhibitors (TKIs) are currently in clinical use and provide unique treatment options for many patients. PTPs on the other hand have long been regarded as “undruggable” and only recently have gained increased attention in drug discovery. Striatal-enriched tyrosine phosphatase (STEP) is a neuron-specific PTP that is overactive in Alzheimer’s disease (AD) and other neurodegenerative and neuropsychiatric disorders, including Parkinson’s disease, schizophrenia, and fragile X syndrome. An emergent model suggests that the increase in STEP activity interferes with synaptic function and contributes to the characteristic cognitive and behavioral deficits present in these diseases. Prior efforts to generate STEP inhibitors with properties that warrant clinical development have largely failed. To identify novel STEP inhibitor scaffolds, we developed a biophysical, label-free high-throughput screening (HTS) platform based on the protein thermal shift (PTS) technology. In contrast to conventional HTS using STEP enzymatic assays, we found the PTS platform highly robust and capable of identifying true hits with confirmed STEP inhibitory activity and selectivity. This new platform promises to greatly advance STEP drug discovery and should be applicable to other PTP targets.


2021 ◽  
pp. 247255522110006
Author(s):  
Michael D. Scholle ◽  
Zachary A. Gurard-Levin

Arginase-1, an enzyme that catalyzes the reaction of L-arginine to L-ornithine, is implicated in the tumor immune response and represents an interesting therapeutic target in immuno-oncology. Initiating arginase drug discovery efforts remains a challenge due to a lack of suitable high-throughput assay methodologies. This report describes the combination of self-assembled monolayers and matrix-assisted laser desorption ionization mass spectrometry to enable the first label-free and high-throughput assay for arginase activity. The assay was optimized for kinetically balanced conditions and miniaturized, while achieving a robust assay (Z-factor > 0.8) and a significant assay window [signal-to-background ratio > 20] relative to fluorescent approaches. To validate the assay, the inhibition of the reference compound nor-NOHA (Nω-hydroxy-nor-L-arginine) was evaluated, and the IC50 measured to be in line with reported results (IC50 = 180 nM). The assay was then used to complete a screen of 175,000 compounds, demonstrating the high-throughput capacity of the approach. The label-free format also eliminates opportunities for false-positive results due to interference from library compounds and optical readouts. The assay methodology described here enables new opportunities for drug discovery for arginase and, due to the assay flexibility, can be more broadly applicable for measuring other amino acid–metabolizing enzymes.


2017 ◽  
Vol 8 (2) ◽  
pp. 536 ◽  
Author(s):  
Dhananjay Kumar Singh ◽  
Caroline C. Ahrens ◽  
Wei Li ◽  
Siva A. Vanapalli

2010 ◽  
Vol 35 (24) ◽  
pp. 4102 ◽  
Author(s):  
Etienne Shaffer ◽  
Corinne Moratal ◽  
Pierre Magistretti ◽  
Pierre Marquet ◽  
Christian Depeursinge

APOPTOSIS ◽  
2014 ◽  
Vol 19 (9) ◽  
pp. 1411-1418 ◽  
Author(s):  
Obaid Aftab ◽  
Madiha Nazir ◽  
Mårten Fryknäs ◽  
Ulf Hammerling ◽  
Rolf Larsson ◽  
...  

2017 ◽  
Vol 89 (17) ◽  
pp. 9002-9008 ◽  
Author(s):  
Miquel Avella-Oliver ◽  
Javier Carrascosa ◽  
Rosa Puchades ◽  
Ángel Maquieira

ACS Omega ◽  
2018 ◽  
Vol 3 (11) ◽  
pp. 14814-14823 ◽  
Author(s):  
Katrin M. Krebs ◽  
Eva M. Pfeil ◽  
Katharina Simon ◽  
Manuel Grundmann ◽  
Felix Häberlein ◽  
...  

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