N-Terminal peptidic boronic acids selectively inhibit human ClpXP

被引：29

作者：

Knott, Kenneth ^{[1
]}

Fishovitz, Jennifer ^{[2
]}

Thorpe, Steven B. ^{[1
]}

Lee, Irene ^{[2
]}

Santos, Webster L. ^{[1
]}

机构：

[1] Virginia Tech, Dept Chem, Blacksburg, VA 24061 USA

[2] Case Western Reserve Univ, Dept Chem, Cleveland, OH 44106 USA

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2010年 / 8卷 / 15期

关键词：

ATP-DEPENDENT PROTEASE; ALPHA; BETA-UNSATURATED CARBONYL-COMPOUNDS; CATALYZED BETA-BORATION; LON PROTEASE; ESCHERICHIA-COLI; ANTIFUNGAL AGENT; TRANSITION-STATE; CHYMOTRYPSIN; DEGRADATION; POTENT;

D O I：

10.1039/c004247a

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The synthesis and development of N-terminal peptidic boronic acids as protease inhibitors is reported. N-Terminal peptidic boronic acids interrogate the S' sites of the target protein for selectivity and provide a new strategy that complements the currently known peptidic alpha-amino boronic acids (C-terminal boronic acids). After screening a series of N-terminal peptidic boronic acids, the first selective inhibitor of human ClpXP, an ATP-dependent serine protease present in the mitochondrial matrix, was discovered. This should facilitate the understanding of the physiological function of this protease

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收藏

页码：3451 / 3456

页数：6

相关论文

共 31 条

[1] Potent and selective inhibitors of the proteasome: Dipeptidyl boronic acids [J].

Adams, J ;

Behnke, M ;

Chen, SW ;

Cruickshank, AA ;

Dick, LR ;

Grenier, L ;

Klunder, JM ;

Ma, YT ;

Plamondon, L ;

Stein, RL .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (04) :333-338

[2] Discovery of a new boron-containing antifungal agent, 5-fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole (AN2690), for the potential treatment of onychomycosis [J].

Baker, Stephen J. ;

Zhang, Yong-Kang ;

Akama, Tsutomu ;

Lau, Agnes ;

Zhou, Huchen ;

Hernandez, Vincent ;

Mao, Weimin ;

Alley, M. R. K. ;

Sanders, Virginia ;

Plattner, Jacob J. .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (15) :4447-4450

[3] Protein degradation in mitochondria: implications for oxidative stress, aging and disease: a novel etiological classification of mitochondrial proteolytic disorders [J].

Bota, DA ;

Davies, KJA .

MITOCHONDRION, 2001, 1 (01) :33-49

[4] Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion [J].

Bulteau, AL ;

Lundberg, KC ;

Ikeda-Saito, M ;

Isaya, G ;

Szweda, LI .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (17) :5987-5991

[5] Identification of the proteasome inhibitor MG262 as a potent ATP-dependent inhibitor of the Salmonella enterica serovar typhimurium lon protease [J].

Frase, Hilary ;

Hudak, Jason ;

Lee, Irene .

BIOCHEMISTRY, 2006, 45 (27) :8264-8274

[6] sp2-sp3 Hybridized Mixed Diboron: Synthesis, Characterization, and Copper-Catalyzed β-Boration of α,β-Unsaturated Conjugated Compounds [J].

Gao, Ming ;

Thorpe, Steven B. ;

Santos, Webster L. .

ORGANIC LETTERS, 2009, 11 (15) :3478-3481

[7]

GARCIANAFRIA J, 2010, PROTEIN SCI

[8] Characterization of peptidyl boronic acid inhibitors of mammalian 20 S and 26 S proteasomes and their inhibition of proteasomes in cultured cells [J].

Gardner, RC ;

Assinder, SJ ;

Christie, G ;

Mason, GGF ;

Markwell, R ;

Wadsworth, H ;

McLaughlin, M ;

King, R ;

Chabot-Fletcher, MC ;

Breton, JJ ;

Allsop, D ;

Rivett, AJ .

BIOCHEMICAL JOURNAL, 2000, 346 :447-454

[9]

GOLDBERG AL, 1994, METHOD ENZYMOL, V244, P350

[10] N-heterocyclic carbenes([+]): Generation under mild conditions and formation of group 8-10 transition metal complexes relevant to catalysis [J].

Herrmann, WA ;

Elison, M ;

Fischer, J ;

Kocher, C ;

Artus, GRJ .

CHEMISTRY-A EUROPEAN JOURNAL, 1996, 2 (07) :772-780

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