Analysis of Subpocket Selectivity and Identification of Potent Selective Inhibitors for Matriptase and Matriptase-2
Dominic Duchêne, Éloïc Colombo, Antoine Désilets, Pierre‐Luc Boudreault, Richard Leduc, Éric Marsault, Rafaël Najmanovich · Journal of Medicinal Chemistry · 2014
We studied the factors affecting the selectivity of peptidomimetic inhibitors of the highly homologous proteases matriptase and matriptase-2 across subpockets using docking simulations. We observed that the farther away a subpocket is located from the catalytic site, the more pronounced its role in selectivity. As a result of our exhaustive virtual screening, we biochemically validated novel potent and selective inhibitors of both enzymes.