D. Alexander Shannon, Dr. Christian Gu, Christopher J. McLaughlin, Dr. Markus Kaiser, Dr. Renier A. L. van der Hoorn and Prof. Eranthie Weerapana
The cover picture shows an artist's rendering of the DAS1 activity-based probe zeroing in on a target model serine protease (bovine α-chymotrypsin, PDB ID: 4CHA) in the context of a complex proteome. Based on the known serine protease inhibitor 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), DAS1 contains a sulfonyl-fluoride electrophile as a warhead and an alkyne to promote versatile analysis. In the communication on p. 2327 ff., R. A. L. van der Hoorn, E. Weerapana, et al. demonstrate that the covalent attachment of DAS1 to active serine proteases allows for subsequent observation and identification of these enzymes by in-gel fluorescence or streptavidin enrichment and mass spectrometry, while retaining the inhibitory efficacy of the parent compound. Furthermore, the small size of the probe facilitates cell permeability. DAS1 provides a valuable proteomic tool for understanding serine protease activation within complex biological systems. The image was created by O'Reilly Science Art using the VMD molecular visualization program (“VMD–Visual Molecular Dynamics”, W. Humphrey, A. Dalke, K. Schulten, J. Mol. Graphics 1996, 14.1, 33–38).