Structure-based design, synthesis and biochemical testing of novel and potent Smac peptido-mimetics

被引：47

作者：

Sun, HY

Nikolovska-Coleska, Z

Chen, JY

Yang, CY

Tomita, Y

Pan, HG

Yoshioka, Y

Krajewski, K

Roller, PP

Wang, SM

机构：

[1] Univ Michigan, Ctr Comprehens Canc, Dept Internal Med, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Ctr Comprehens Canc, Dept Med Chem, Ann Arbor, MI 48109 USA

[3] Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20057 USA

[4] NCI, Frederick Canc Res & Dev Ctr, Med Chem Lab, Frederick, MD 21702 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 03期

关键词：

Smac; peptido-mimetics; XIAP;

D O I：

10.1016/j.bmcl.2004.11.008

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Structure-based design, chemical synthesis and biochemical testing of a series of novel Smac peptido-mimetics as inhibitors of XIAP protein are described. The most potent compound, 6j, has a binding affinity (K-i value) of 24 nM to XIAP BIR3 protein and is 24 times more potent than the native Smac AVPI peptide. Further optimization of these potent Smac mimetics may ultimately lead to the development of a novel class of anticancer drugs for the treatment of human cancer by overcoming apoptosis-resistance of cancer cells through targeting the inhibitor of apoptosis proteins. (C) 2004 Elsevier Ltd. All rights reserved.

引用

收藏

页码：793 / 797

页数：5

相关论文

共 21 条

[1] Synthetic Smac/DIABLO peptides enhance the effects of chemotherapeutic agents by binding XIAP and cIAP1 in situ [J].

Arnt, CR ;

Chiorean, MV ;

Heldebrant, MV ;

Gores, GJ ;

Kaufmann, SH .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (46) :44236-44243

[2] IAP family proteins - suppressors of apoptosis [J].

Deveraux, QL ;

Reed, TC .

GENES & DEVELOPMENT, 1999, 13 (03) :239-252

[3] Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition [J].

Du, CY ;

Fang, M ;

Li, YC ;

Li, L ;

Wang, XD .

CELL, 2000, 102 (01) :33-42

[4] DIABLO promotes apoptosis by removing MIHA/XIAP from processed caspase 9 [J].

Ekert, PG ;

Silke, J ;

Hawkins, CJ ;

Verhagen, AM ;

Vaux, DL .

JOURNAL OF CELL BIOLOGY, 2001, 152 (03) :483-490

[5] Smac agonists sensitize for Apo2L/TRAIL- or anticancer drug-induced apoptosis and induce regression of malignant glioma in vivo [J].

Fulda, S ;

Wick, W ;

Weller, M ;

Debatin, KM .

NATURE MEDICINE, 2002, 8 (08) :808-815

[6]

Huang YH, 2001, CELL, V104, P781, DOI 10.1016/S0092-8674(02)02075-5

[7] APOPTOSIS - BASIC BIOLOGICAL PHENOMENON WITH WIDE-RANGING IMPLICATIONS IN TISSUE KINETICS [J].

KERR, JFR ;

WYLLIE, AH ;

CURRIE, AR .

BRITISH JOURNAL OF CANCER, 1972, 26 (04) :239-+

[8] Molecular targeting of inhibitor of apoptosis proteins based on small molecule mimics of natural binding partners [J].

Kipp, RA ;

Case, MA ;

Wist, AD ;

Cresson, CM ;

Carrell, M ;

Griner, E ;

Wiita, A ;

Albiniak, PA ;

Chai, JJ ;

Shi, YG ;

Semmelhack, MF ;

McLendon, GL .

BIOCHEMISTRY, 2002, 41 (23) :7344-7349

[9] Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain [J].

Liu, ZH ;

Sun, CH ;

Olejniczak, ET ;

Meadows, RP ;

Betz, SF ;

Oost, T ;

Herrmann, J ;

Wu, JC ;

Fesik, SW .

NATURE, 2000, 408 (6815) :1004-1008

[10] Development and optimization of a binding assay for the XIAP BIR3 domain using fluorescence polarization [J].

Nikolovska-Coleska, Z ;

Wang, RX ;

Fang, XL ;

Pan, HG ;

Tomita, Y ;

Li, P ;

Roller, PP ;

Krajewski, K ;

Saito, NG ;

Stuckey, JA ;

Wang, SM .

ANALYTICAL BIOCHEMISTRY, 2004, 332 (02) :261-273