Mutasynthesis of fluorosalinosporamide, a potent and reversible inhibitor of the proteasome

被引：87

作者：

Eustaquio, Alessandra S.

Moore, Bradley S. ^{[1
]}

机构：

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

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2008年 / 47卷 / 21期

关键词：

cancer; fluorine; halogenation; mutasynthesis; proteasome; salinosporamide;

D O I：

10.1002/anie.200800177

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A knockout result: Fluorine substituents give drugs beneficial properties. By using a rational combination of genetic engineering and precursor-directed biosynthesis, fluorosalinosporamide (see scheme) was generated in a fermentation-based approach. The anticancer lead compound and marine natural product salinosporamide A is chlorinated. A comparison of the biological activity of these proteasome inhibitors is presented. (Chemical Equation Presented). © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

引用

收藏

页码：3936 / 3938

页数：3

相关论文

共 23 条

[1] An improved synthesis of 5′-fluoro-5′-deoxyadenosines [J].

Ashton, TD ;

Scammells, PJ .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (14) :3361-3363

[2] Biosynthetic convergence of salinosporamides A and B in the marine actinomycete Salinispora tropica [J].

Beer, Laura L. ;

Moore, Bradley S. .

ORGANIC LETTERS, 2007, 9 (05) :845-848

[3] Fluorine in medicinal chemistry [J].

Böhm, HJ ;

Banner, D ;

Bendels, S ;

Kansy, M ;

Kuhn, B ;

Müller, K ;

Obst-Sander, U ;

Stahl, M .

CHEMBIOCHEM, 2004, 5 (05) :637-643

[4] A novel orally active proteasome inhibitor induces apoptosis in multiple myeloma cells with mechanisms distinct from Bortezomib [J].

Chauhan, D ;

Catley, L ;

Li, GL ;

Podar, K ;

Hideshima, T ;

Velankar, M ;

Mitsiades, C ;

Mitsiades, N ;

Yasui, H ;

Letai, A ;

Ovaa, H ;

Berkers, C ;

Nicholson, B ;

Chao, TH ;

Neuteboom, STC ;

Richardson, P ;

Palladino, MA ;

Anderson, KC .

CANCER CELL, 2005, 8 (05) :407-419

[5] Fluorometabolite biosynthesis and the fluorinase from Streptomyces cattleya [J].

Deng, H ;

O'Hagan, D ;

Schaffrath, C .

NATURAL PRODUCT REPORTS, 2004, 21 (06) :773-784

[6] Crystal structure and mechanism of a bacterial fluorinating enzyme [J].

Dong, CJ ;

Huang, FL ;

Deng, H ;

Schaffrath, C ;

Spencer, JB ;

O'Hagan, D ;

Naismith, JH .

NATURE, 2004, 427 (6974) :561-565

[7] Discovery and characterization of a marine bacterial SAM-dependent chlorinase [J].

Eustaquio, Alessandra S. ;

Pojer, Florence ;

Noel, Joseph P. ;

Moore, Bradley S. .

NATURE CHEMICAL BIOLOGY, 2008, 4 (01) :69-74

[8]

Feling R. H., 2003, ANGEW CHEM, V115, P369

[9] Salinosporamide A:: A highly cytotoxic proteasome inhibitor from a novel microbial source, a marine bacterium of the new genus Salinospora [J].

Feling, RH ;

Buchanan, GO ;

Mincer, TJ ;

Kauffman, CA ;

Jensen, PR ;

Fenical, W .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2003, 42 (03) :355-+

[10] Crystal structures of salinosporamide A (NPI-0052) and B (NPI-0047) in complex with the 20S proteasome reveal important consequences of β-lactone ring opening and a mechanism for irreversible binding [J].

Groll, M ;

Huber, R ;

Potts, BCM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (15) :5136-5141