Discovery of a Cryptic Depsipeptide from Streptomyces ghanaensis via MALDI‐MS‐Guided High‐Throughput Elicitor Screening

2020 ◽  
Vol 59 (51) ◽  
pp. 23005-23009
Author(s):  
Chen Zhang ◽  
Mohammad R. Seyedsayamdost
2015 ◽  
Vol 14 (12) ◽  
pp. 5088-5098 ◽  
Author(s):  
Bas C. Jansen ◽  
Karli R. Reiding ◽  
Albert Bondt ◽  
Agnes L. Hipgrave Ederveen ◽  
Magnus Palmblad ◽  
...  

2017 ◽  
Vol 22 (10) ◽  
pp. 1203-1210 ◽  
Author(s):  
Katrin Beeman ◽  
Jens Baumgärtner ◽  
Manuel Laubenheimer ◽  
Karlheinz Hergesell ◽  
Martin Hoffmann ◽  
...  

Mass spectrometry (MS) is known for its label-free detection of substrates and products from a variety of enzyme reactions. Recent hardware improvements have increased interest in the use of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS for high-throughput drug discovery. Despite interest in this technology, several challenges remain and must be overcome before MALDI-MS can be integrated as an automated “in-line reader” for high-throughput drug discovery. Two such hurdles include in situ sample processing and deposition, as well as integration of MALDI-MS for enzymatic screening assays that usually contain high levels of MS-incompatible components. Here we adapt our c-MET kinase assay to optimize for MALDI-MS compatibility and test its feasibility for compound screening. The pros and cons of the Echo (Labcyte) as a transfer system for in situ MALDI-MS sample preparation are discussed. We demonstrate that this method generates robust data in a 1536-grid format. We use the MALDI-MS to directly measure the ratio of c-MET substrate and phosphorylated product to acquire IC50 curves and demonstrate that the pharmacology is unaffected. The resulting IC50 values correlate well between the common label-based capillary electrophoresis and the label-free MALDI-MS detection method. We predict that label-free MALDI-MS-based high-throughput screening will become increasingly important and more widely used for drug discovery.


2017 ◽  
Vol 22 (10) ◽  
pp. 1246-1252 ◽  
Author(s):  
Kishore Kumar Jagadeesan ◽  
Simon Ekström

Recently, mass spectrometry (MS) has emerged as an important tool for high-throughput screening (HTS) providing a direct and label-free detection method, complementing traditional fluorescent and colorimetric methodologies. Among the various MS techniques used for HTS, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) provides many of the characteristics required for high-throughput analyses, such as low cost, speed, and automation. However, visualization and analysis of the large datasets generated by HTS MALDI-MS can pose significant challenges, especially for multiparametric experiments. The datasets can be generated fast, and the complexity of the experimental data (e.g., screening many different sorbent phases, the sorbent mass, and the load, wash, and elution conditions) makes manual data analysis difficult. To address these challenges, a comprehensive informatics tool called MALDIViz was developed. This tool is an R-Shiny-based web application, accessible independently of the operating system and without the need to install any program locally. It has been designed to facilitate easy analysis and visualization of MALDI-MS datasets, comparison of multiplex experiments, and export of the analysis results to high-quality images.


Talanta ◽  
2021 ◽  
Vol 222 ◽  
pp. 121495
Author(s):  
Wei Wang ◽  
Anna Kałuża ◽  
Jan Nouta ◽  
Simone Nicolardi ◽  
Mirosława Ferens-Sieczkowska ◽  
...  

2014 ◽  
Vol 50 (90) ◽  
pp. 13960-13962 ◽  
Author(s):  
Zhenzhen Deng ◽  
Mingliang Ye ◽  
Yangyang Bian ◽  
Zheyi Liu ◽  
Fangjie Liu ◽  
...  

A multiplex isotope dimethyl labeling approach allowed MALDI MS to monitor the time dependent consumption of substrates and generation of products in one spot.


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