Synthesis and extended activity of triazole-containing macrocyclic protease inhibitors
Research output: Contribution to journal › Journal article › Research › peer-review
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 language | English |
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Journal | Chemistry: A European Journal |
Volume | 19 |
Issue number | 24 |
Pages (from-to) | 7975-7981 |
Number of pages | 7 |
ISSN | 0947-6539 |
DOIs | |
Publication status | Published - 10 Jun 2013 |
ID: 49635195