Rapid synthesis of internal peptidyl α-ketoamides by on resin oxidation for the construction of rhomboid protease inhibitors

Rhomboid proteases are intramembrane serine proteases, which are involved in a wide variety of biological processes and have been implied in various human diseases. Recently, peptidyl α-ketoamides have been reported as rhomboid inhibitors with high potency and selectivity - owing to their interaction with both the primed and non-primed site of the target protease. However, their synthesis has been performed by solution phase chemistry. Here, we report a solid phase strategy towards ketoamides as rhomboid protease inhibitors, allowing rapid synthesis and optimization. We found that the primed site binding part of inhibitors is crucial for potency.

Jaar van publicatie:2021

BOF-keylabel:ja

IOF-keylabel:ja

BOF-publication weight:1

CSS-citation score:1

Auteurs:International

Authors from:Higher Education

Toegankelijkheid:Open