3-Cyano-3-aza-β-amino Acid Derivatives as Inhibitors of Human Cysteine Cathepsins
- Nitrile-type inhibitors are known to interact with cysteine proteases in a covalent-reversible manner. The chemotype of 3-cyano-3-aza-β-amino acid derivatives was designed in which the N-cyano group is centrally arranged in the molecule to allow for interactions with the nonprimed and primed binding regions of the target enzymes. These compounds were evaluated as inhibitors of the human cysteine cathepsins K, S, B, and L. They exhibited slow-binding behavior and were found to be exceptionally potent, in particular toward cathepsin K, with second-order rate constants up to 52 900 × 103 M–1 s–1.
Document Type: | Article |
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Language: | English |
Author: | Janina Schmitz, Anna-Madeleine Beckmann, Adela Dudic, Tianwei Li, Robert Sellier, Ulrike Bartz, Michael Gütschow |
Parent Title (English): | ACS Medicinal Chemistry Letters |
Volume: | 5 |
Issue: | 10 |
First Page: | 1076 |
Last Page: | 1081 |
ISSN: | 1948-5875 |
URN: | urn:nbn:de:hbz:1044-opus-13258 |
DOI: | https://doi.org/10.1021/ml500238q |
PMID: | https://pubmed.ncbi.nlm.nih.gov/25313316 |
Publisher: | ACS Publications |
Publishing Institution: | Hochschule Bonn-Rhein-Sieg |
Date of first publication: | 2014/09/03 |
Funding: | J.S. is supported by the Gender Equality Center of the Bonn-Rhein-Sieg University of Applied Sciences. |
Keyword: | cysteine proteases; human cathepsins; nitrile inhibitors; β-amino acids |
Departments, institutes and facilities: | Fachbereich Angewandte Naturwissenschaften |
Dewey Decimal Classification (DDC): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 615 Pharmakologie, Therapeutik | |
Entry in this database: | 2015/04/02 |
Licence (English): | ACS AuthorChoice/Editors’ Choice License |