Grassystatin-derived peptides selectively inhibit cathepsin E and have low affinity to cathepsin D.

Sophie Stotz, Daniel Bleher, Hubert Kalbacher, Andreas Maurer

Biochemical and biophysical research communications 2020 Jun 18

filter terms:

Aspartic proteases are important biomarkers of human disease and interesting targets for modulation of immune response via MHC class II antigen processing inhibition. The lack of inhibitors with sufficient selectivity hampers precise analysis of the role of cathepsin E and napsin A in samples containing the ubiquitous and highly abundant homolog cathepsin D. Grassystatins from marine cyanobacteria show promising selectivity for cathepsin E but contain several ester bonds that make their synthesis cumbersome and thus limit availability of the inhibitors. Herewith, we present grassystatin-derived cathepsin E inhibitors with greatly facilitated synthesis but retained selectivity profile. We demonstrate their affinity and selectivity with both enzyme kinetic assays and streptavidin-based pull-down from cells and mouse organs. Our findings suggest that grassystatin-like inhibitors are useful tools for targeted inhibition of cathepsin E and thus provide a novel approach for cancer and immunology research. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Sophie Stotz, Daniel Bleher, Hubert Kalbacher, Andreas Maurer. Grassystatin-derived peptides selectively inhibit cathepsin E and have low affinity to cathepsin D. Biochemical and biophysical research communications. 2020 Jun 18;527(1):238-241