A collaboration led by Prof Lizbeth Hedstrom (Brandeis University, US) reported in Bioorganic & Medicinal Chemistry Letters a series of diarylcarbonates as promiscuous deubiquitinating enzyme (DUB) inhibitor. In contrast to other promiscuous inhibitors, the reported class of diarylcarbonate inhibitors shows a relatively small off-target spectrum and does not induce insoluble ubiquitin aggregates. Overall, the diarylcarbonates serve as valuable research tools for the study of regulatory pathways, stabilizing lysates and as starting points for the design of more selective DUB inhibitors.

Diarylcarbonates are a new class of deubiquitinating enzyme inhibitor.

Marcus J.C.Long (a), Ann P.Lawson (b), Rick Baggio (a), Yu Qian (c), Lior Rozhansky (b), Domenico Fasci (d), Farid El Oualid (e), Eranthie Weerapana (c), LizbethHedstrom (b, f)

a) Graduate Program in Biochemistry and Biophysics Brandeis University, 415 South Street, Waltham, MA 02453, USA
b) Department of Biology, Brandeis University, 415 South Street, Waltham, MA 02453, USA
c) Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA
d) Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Road, La Jolla, CA 92037, USA
e) UbiQ Bio BV, Science Park 408, 1098 XH Amsterdam, the Netherlands
f) Department of Chemistry3, Brandeis University, 415 South Street, Waltham, MA 02453, USA0

https://www.sciencedirect.com/science/article/pii/S0960894X18309314