Synthesis and extended activity of triazole-containing macrocyclic protease inhibitors

Ashok D Pehere, Markus Pietsch, Michael Gütschow, Paul M. Neilsen, Daniel Sejer Pedersen, Steven Nguyen, Ondrej Zvarec, Matthew J. Sykes, David F. Callen, Andrew D. Abell

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)7975-7981
Number of pages7
JournalChemistry - A European Journal
Issue number24
StatePublished - Jun 10 2013


  • NMR spectroscopy
  • click chemistry
  • macrocycles
  • peptidomimetics
  • protease inhibitors


Dive into the research topics of 'Synthesis and extended activity of triazole-containing macrocyclic protease inhibitors'. Together they form a unique fingerprint.

Cite this