Fragment-Based Drug Discovery: Comparing Labeled and Label-Free Screening of β-Amyloid Secretase (BACE-1) Using Fluorescence Spectroscopy and Ultrafast SPE/MS/MS

In this application note β-amyloid secretase (BACE-1) is screened against a fragment library using two substrates, a labeled and an unlabeled peptide, which were detected either by FS or ultrafast SPE/MS/MS using the Agilent RapidFire High-throughput Mass Spectrometry (MS) System. Different kinetic parameters, hit rates, and hit sets were obtained depending on the substrate and detection method, suggesting that using fluorescent labels and optical detection methods can lead to follow-up of compounds that are inactive against the unlabeled, more biologically relevant substrate.