Small-Molecule Inhibitors and Probes for Ubiquitin- and Ubiquitin-Like-Specific Proteases

• Published in: Chembiochem : a European journal of chemical biology Vol. 6; no. 2; pp. 287 - 291
• Main Authors: Borodovsky, Anna, Ovaa, Huib, Meester, Wim J.N, Venanzi, Emily S, Bogyo, Matthew S, Hekking, Brian G, Ploegh, Hidde L, Kessler, Benedikt M, Overkleeft, Herman S
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01.02.2005; WILEY-VCH Verlag; WILEY‐VCH Verlag
• Subjects: active-site-directed probe; Amino Acid Sequence; Endopeptidases - chemistry; Endopeptidases - genetics; Endopeptidases - metabolism; enzymes; Molecular Structure; Peptides - chemistry; Peptides - genetics; Peptides - metabolism; Protease Inhibitors - metabolism; proteases; protein modifications; Protein Processing, Post-Translational; Sulfones - chemistry; SUMO APG; SUMO-1 Protein - genetics; SUMO-1 Protein - metabolism; ubiquitin; Ubiquitin - chemistry; Ubiquitin - genetics; Ubiquitin - metabolism; Ubiquitin-Specific Proteases; Vinyl Compounds - chemistry; vinyl sulfones
• ISSN: 1439-4227; 1439-7633
• DOI: 10.1002/cbic.200400236

There's always a catch. The post‐translational modification of proteins with ubiquitin (Ub) or ubiquitin‐like (Ubl) modifiers is an important signal in the regulation of a variety of biological processes, such as degradation and regulation of gene expression. Here we report the synthesis of a panel of peptide vinyl sulfones (see scheme) harboring various portions of the Ub C terminus by using a safety‐catch linker. Depending on their length, such compounds can efficiently target Ubl‐specific proteases.