Function-Oriented Biosynthesis of β-Lactone Proteasome Inhibitors in Salinispora tropica

被引：57

作者：

Nett, Markus

Guider, Tobias A. M.

Kale, Andrew J.

Hughes, Chambers C.

Moore, Bradley S. ^{[1
]}

机构：

[1] Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 19期

关键词：

SALINOSPORAMIDE-A; 20S PROTEASOME; CANCER-THERAPY; POTENT; ANTIPROTEALIDE; LACTACYSTIN; MECHANISM; OMURALIDE; UBIQUITIN; NPI-0052;

D O I：

10.1021/jm901098m

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The natural proteasome inhibitor salinosporamide A from the marine bacterium Salinispora tropica is a promising drug candidate for the treatment of multiple myeloma and mantle cell lymphoma. Using a comprehensive approach that combined chemical synthesis with metabolic engineering, we generated a series of salinosporamide analogues with altered proteasome binding affinity. One of the engineered compounds is equipotent to salinosporamide A in inhibition of the chymotrypsin-like activity of. the proteasome yet exhibits superior activity in the cell-based HCT-116 assay.

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收藏

页码：6163 / 6167

页数：5

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