1359968-98-1Relevant articles and documents
Synthesis and extended activity of triazole-containing macrocyclic protease inhibitors
Pehere, Ashok D.,Pietsch, Markus,Gütschow, Michael,Neilsen, Paul M.,Pedersen, Daniel Sejer,Nguyen, Steven,Zvarec, Ondrej,Sykes, Matthew J.,Callen, David F.,Abell, Andrew D.
, p. 7975 - 7981 (2013/07/11)
Peptide-derived protease inhibitors are an important class of compounds with the potential to treat a wide range of diseases. Herein, we describe the synthesis of a series of triazole- containing macrocyclic protease inhibitors pre-organized into a b-strand conformation and an evaluation of their activity against a panel of proteases. Acyclic azidoalkyne-based aldehydes are also evaluated for comparison. The macrocyclic peptidomimetics showed considerable activity towards calpain II, cathepsin L and S, and the 20S proteasome chymotrypsin-like activity. Some of the first examples of highly potent macrocyclic inhibitors of cathepsin S were identified. These adopt a well-defined b-strand geometry as shown by NMR spectroscopy, X-ray analysis, and molecular docking studies.
New β-strand templates constrained by Huisgen cycloaddition
Pehere, Ashok D.,Abell, Andrew D.
, p. 1330 - 1333 (2012/05/20)
New peptidic templates constrained into a β-strand geometry by linking acetylene and azide containing P1 and P3 residues of a tripeptide by Huisgen cycloaddition are presented. The conformations of the macrocycles are defined by NMR studies and those that best define a β-strand are shown to be potent inhibitors of the protease calpain. The β-strand templates presented and defined here are prepared under optimized conditions that should be suitable for targeting a range of proteases and other applications requiring such a geometry.
