After spending an amazing time with my new-born daughter, I am back at work since a couple of weeks. My first official working day as a mom started by bringing my daughter to daycare and wiping away some tears. Once arrived at work, it was nice to be back, catching up with colleagues, doing science, and contributing to a solution against the COVID-19 pandemic.
Although I couldn’t support the COVID-19 program during my maternity leave, I am now again in the lead of this project to follow up on the compounds selected from the screen earlier this year. After two deselection assays and running dose response curves, we picked the actives with a specialized team of medicinal chemists. We are now close to finalizing this project and hopefully soon we will have valuable compound leads for follow-up studies.
For the selection process of the COVID-19 actives, one of the assays was based on a Mass Spectrometry read-out. In our ultra-High-Throughput Screening (uHTS) platform, we have integrated the rapifleX MALDI PharmaPulse® (Bruker), a matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), and we presented this in a couple of webinars. Ionization of analytes by MALDI-TOF is based on the absorption of the laser energy by a matrix and can be used to detect biomolecules. In order to prepare the samples, the CyBio Well vario from Analytik Jena is also integrated in our uHTS platform that is able to spot the matrix and sample, using one of the spotting protocols in 1536-well format. The mass spectra generated by the rapifleX are automatically analyzed by the PharmaPulse® software and then uploaded to our database to select the actives. The field of MALDI-TOF based high throughput screening is now rapidly growing and expanding for many different HTS assays. In my next blog, I will summarize and reflect on the pro’s and con’s of using mass spectrometry in a screening setup and highlight future developments.