Convergent Synthesis and Biological Evaluation of Syringolin A and Derivatives as Eukaryotic 20S Proteasome Inhibitors

被引：51

作者：

Clerc, Jerome ^{[1
]}

Schellenberg, Barbara ^{[2
]}

Groll, Michael ^{[3
]}

Bachmann, Andre S. ^{[4
]}

Huber, Robert ^{[5
,6
,7
]}

Dudler, Robert ^{[2
]}

Kaiser, Markus ^{[1
]}

机构：

[1] Max Planck Gesell, Chem Genom Ctr, D-44227 Dortmund, Germany

[2] Univ Zurich, Inst Plant Biol, Zurich Basel Plant Sci Ctr, CH-8008 Zurich, Switzerland

[3] Tech Univ Munich, Dept Chem, CIPSM, D-85747 Garching, Germany

[4] Univ Hawaii Manoa, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA

[5] Max Planck Inst Biochem, D-82152 Martinsried, Germany

[6] Univ Duisburg Essen, Zentrum Med Biotechnol, D-45117 Essen, Germany

[7] Cardiff Univ, Cardiff CF10 3US, S Glam, Wales

来源：

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | 2010年 / 2010卷 / 21期

基金：

瑞士国家科学基金会;

关键词：

Synthetic methods; Natural products; Biological activity; Metathesis; Inhibitors; TMC-95A ANALOGS; PV.-SYRINGAE; ESTERS; ACIDS; CLEAVAGE; POTENT; YEAST;

D O I：

10.1002/ejoc.201000317

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A convergent synthesis of SylA was developed and consists of the synthesis of a fully functionalized macrocycle, which is subsequently coupled with a urea moiety. For cyclization, ring-closing metathesis of a conformationally preorganized precursor was employed. The established synthetic route was then applied to the synthesis of SylA derivatives by using various peptidic side chains for decoration of the SylA macrocycle. The resulting collection of SylA analogues was tested for proteasome inhibition, revealing PEGylated SylA derivatives as the most potent proteasome inhibitors.

引用

页码：3991 / 4003

页数：13

共 46 条

[1] Functional analysis of genes involved in the synthesis of syringolin A by Pseudomonas syringae pv. syringae B301D-R [J].

Amrein, H ;

Makart, S ;

Granado, J ;

Shakya, R ;

Schneider-Pokorny, J ;

Dudler, R .

MOLECULAR PLANT-MICROBE INTERACTIONS, 2004, 17 (01) :90-97

[2] OXIDATION OF ALPHA,BETA-UNSATURATED ALDEHYDES [J].

BAL, BS ;

CHILDERS, WE ;

PINNICK, HW .

TETRAHEDRON, 1981, 37 (11) :2091-2096

[3] A stereoselective synthesis of phosphinic acid phosphapeptides corresponding to glutamyl-γ-glutamate and incorporation into potent inhibitors of folylpoly-γ-glutamyl synthetase [J].

Bartley, DM ;

Coward, JK .

JOURNAL OF ORGANIC CHEMISTRY, 2005, 70 (17) :6757-6774

[4]

Berkowitz DB, 1996, SYNTHESIS-STUTTGART, P39, DOI 10.1055/s-1996-4177

[5] Syringolin A Selectively Labels the 20 S Proteasome in Murine EL4 and Wild-Type and Bortezomib-Adapted Leukaemic Cell Lines [J].

Clerc, Jerome ;

Florea, Bogdan I. ;

Kraus, Marianne ;

Groll, Michael ;

Huber, Robert ;

Bachmann, Andre S. ;

Dudler, Robert ;

Driessen, Christoph ;

Overkleeft, Herman S. ;

Kaiser, Markus .

CHEMBIOCHEM, 2009, 10 (16) :2638-2643

[6] Synthetic and structural studies on syringolin A and B reveal critical determinants of selectivity and potency of proteasome inhibition [J].

Clerc, Jerome ;

Groll, Michael ;

Illich, Damir J. ;

Bachmann, Andre S. ;

Huber, Robert ;

Schellenberg, Barbara ;

Dudler, Robert ;

Kaiser, Markus .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (16) :6507-6512

[7] Syringolin A, a new plant elicitor from the phytopathogenic bacterium Pseudomonas syringae pv. syringae, inhibits the proliferation of neuroblastoma and ovarian cancer cells and induces apoptosis [J].

Coleman, C. S. ;

Rocetes, J. P. ;

Park, D. J. ;

Wallick, C. J. ;

Warn-Cramer, B. J. ;

Michel, K. ;

Dudler, R. ;

Bachmann, A. S. .

CELL PROLIFERATION, 2006, 39 (06) :599-609

[8] DIASTEREOSELECTIVE ADDITION OF VINYL ORGANOMETALLIC REAGENTS TO L-SERINAL [J].

COLEMAN, RS ;

CARPENTER, AJ .

TETRAHEDRON LETTERS, 1992, 33 (13) :1697-1700

[9] A NEW, STEREOSPECIFIC OLEFIN SYNTHESIS FROM 1,2-DIOLS [J].

COREY, EJ ;

WINTER, RAE .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1963, 85 (17) :2677-&

[10] SYNTHESIS OF ALPHA-HYDROXY STATINE THROUGH A FACIALLY SELECTIVE OSMYLATION OF A CHIRAL ALPHA-AMIDO CROTONATE [J].

DEE, MF ;

ROSATI, RL .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1995, 5 (09) :949-952

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