A Coumarin- Labeled Vinyl Sulfone as Tripeptidomimetic Activity- Based Probe for Cysteine Cathepsins

被引：50

作者：

Mertens, Matthias D. ^{[1
]}

Schmitz, Janina ^{[1
]}

Horn, Martin ^{[2
]}

Furtmann, Norbert ^{[1
,3
]}

Bajorath, Juergen ^{[3
]}

Mares, Michael ^{[2
]}

Guetschow, Michael ^{[1
]}

机构：

[1] Univ Bonn, Inst Pharmaceut, D-53121 Bonn, Germany

[2] Acad Sci Czech Republ, Inst Organ Chem & Biochem, CR-16610 Prague, Czech Republic

[3] Univ Bonn, Bonn Aachen Int Ctr Informat Technol, D-53113 Bonn, Germany

来源：

CHEMBIOCHEM | 2014年 / 15卷 / 07期

关键词：

activity-based probes; cathepsins; coumarins; fluorescent probes; inhibitors; peptidyl vinyl sulfones; LIQUID-CHROMATOGRAPHY; CRYSTAL-STRUCTURES; SMALL-MOLECULE; AMINO-ACIDS; S ACTIVITY; INHIBITORS; SPECIFICITY; PROTEASES; TARGET; DERIVATIZATION;

D O I：

10.1002/cbic.201300806

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A coumarin-tetrahydroquinoline hydride 8 was synthesized as a chemical tool for fluorescent labeling. The rigidified tricyclic coumarin structure was chosen for its suitable fluorescence properties. The connection of 8 with a vinyl sulfone building block was accomplished by convergent synthesis thereby leading to the coumarin-based, tripeptidomimetic activity-based probe 10, containing a Gly-Phe-Gly motif. Probe 10 was evaluated as inactivator of the therapeutically relevant human cysteine cathepsins S, L, K, and B: it showed particularly strong inactivation of cathepsin S. The detection of recombinant and native cathepsin S was demonstrated by applying 10 to in-gel fluorescence imaging.

引用

页码：955 / 959

页数：5

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