Peptido Sulfonyl Fluorides as New Powerful Proteasome Inhibitors

被引：69

作者：

Brouwer, Arwin J. ^{[1
]}

Jonker, Anika ^{[1
]}

Werkhoven, Paul ^{[1
]}

Kuo, Ethan ^{[2
]}

Li, Nan ^{[2
]}

Gallastegui, Nerea ^{[3
]}

Kernmink, Johan ^{[1
]}

Florea, Bogdan I. ^{[2
]}

Groll, Michael ^{[3
]}

Overkleeft, Herman S. ^{[2
]}

Liskamp, Rob M. J. ^{[1
]}

机构：

[1] Univ Utrecht, Fac Sci, Utrecht Inst Pharmaceut Sci, Dept Med Chem & Chem Biol, NL-3508 TB Utrecht, Netherlands

[2] Leiden Univ, Leiden Inst Chem, NL-2300 RA Leiden, Netherlands

[3] Tech Univ Munich, Lehrstuhl Biochem, Dept Chem, Ctr Integrated Prot Sci, D-85748 Garching, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 55卷 / 24期

关键词：

POTENT;

D O I：

10.1021/jm301443r

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new class of potent proteasome inhibitors is described, of which the members contain an amino acid inspired sulfonyl fluoride as the electrophilic trap. In total, 24 peptido sulfonyl fluoride inhibitors have been designed and synthesized, which were inspired by the backbone sequences of the proteasome inhibitors bortezomib, epoxomicin, and Cbz-Leu(3)-aldehyde. Nine of them were very potent proteasome inhibitors, the best of which had an IC50 of 7 nM. A number of the peptido sulfonyl fluoride inhibitors were found to be highly selective for the beta 5 proteasome subunit.

引用

页码：10995 / 11003

页数：9

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