In situ observation of particle-induced desorption from a self-assembled monolayer by laser-ionization mass spectrometry

2003 ◽  
Vol 82 (7) ◽  
pp. 1114-1116 ◽  
Author(s):  
E. Vandeweert ◽  
J. Bastiaansen ◽  
F. Vervaecke ◽  
P. Lievens ◽  
R. E. Silverans ◽  
...  
2020 ◽  
Vol 182 ◽  
pp. 104924 ◽  
Author(s):  
Zachary A. Gurard-Levin ◽  
Cheng Liu ◽  
Andreas Jekle ◽  
Ruchika Jaisinghani ◽  
Suping Ren ◽  
...  

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.


2009 ◽  
Vol 2 (1) ◽  
pp. 119-151 ◽  
Author(s):  
J. P. Kercher ◽  
T. P. Riedel ◽  
J. A. Thornton

Abstract. We report a new method for the simultaneous in situ detection of nitryl chloride (ClNO2) and dinitrogen pentoxide (N2O5) using chemical ionization mass spectrometry (CIMS). The technique relies on the formation and detection of iodide ion-molecule clusters, I(ClNO2)− and I(N2O5)−. The novel N2O5 detection scheme is direct. It does not suffer from high and variable chemical interferences, which are associated with the typical method of nitrate anion detection. We address the role of water vapor, electric field strength, and instrument zero determinations, which influence the overall sensitivity and detection limit of this method. For both species, the method demonstrates high sensitivity (>1 Hz/pptv), precision (~10% for 100 pptv in 1 s), and accuracy (~20%), the latter ultimately determined by the nitrogen dioxide (NO2) cylinder calibration standard and characterization of inlet effects. For the typically low background signals (<10 Hz) and high selectivity, we estimate signal-to-noise (S/N) ratios of 2 for 1 pptv in 60 s averages, but uncertainty associated with the instrumental zero currently leads to an ultimate detection limit of ~5 pptv for both species. We validate our approach for the simultaneous in situ measurement of ClNO2 and N2O5 while on board the Research Vessel (RV) Knorr as part of the ICEALOT 2008 Field Campaign.


Author(s):  
Sankha S. Basu ◽  
Madison H. McMinn ◽  
Begoña Giménez-Cassina Lopéz ◽  
Michael S. Regan ◽  
Elizabeth C. Randall ◽  
...  

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