A Template-Based Approach to Inhibitors of Calpain 2, 20S Proteasome, and HIV-1 Protease

• Published in: ChemMedChem Vol. 8; no. 12; pp. 1918 - 1921
• Main Authors: Jones, Seth A., Neilsen, Paul M., Siew, Limei, Callen, David F., Goldfarb, Nathan E., Dunn, Ben M., Abell, Andrew D.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.12.2013; WILEY‐VCH Verlag; Wiley
• Subjects: Calpain - antagonists & inhibitors; Calpain - metabolism; Catalytic Domain; Cell Line; Cell Survival - drug effects; Chemistry, Medicinal; HCT116 Cells; HIV Protease - chemistry; HIV Protease - metabolism; Humans; inhibitors; Life Sciences & Biomedicine; Macrocyclic Compounds - chemistry; Macrocyclic Compounds - metabolism; Macrocyclic Compounds - toxicity; Peptidomimetics; Pharmacology & Pharmacy; Protease Inhibitors - chemistry; Protease Inhibitors - metabolism; Protease Inhibitors - toxicity; proteases; Proteasome Endopeptidase Complex - chemistry; Proteasome Endopeptidase Complex - metabolism; Protein Binding; Protein Structure, Secondary; Science & Technology; templates; β-strands; inhibitors; proteases; templates; beta-strands; peptidomimetics; BORTEZOMIB; FAMILY; β-strands
• ISSN: 1860-7179; 1860-7187
• DOI: 10.1002/cmdc.201300387

Specificity counts: A template‐based approach to protease inhibitors is presented using a core macrocycle that presents a generic β‐strand template for binding to protease active sites. This is then specifically functionalized at P2, and the C and N termini to give inhibitors of calpain 2, 20S proteasome, and HIV‐1 protease.