Synthesis and activity of tyropeptin A derivatives as potent and selective inhibitors of mammalian 20S proteasome

被引：21

作者：

Momose, I

Umezawa, Y

Hirosawa, S

Iijima, M

Iinuma, H

Ikeda, D

机构：

[1] Microbial Chem Res Ctr, Numazu Biomed Res Inst, Shizuoka 4100301, Japan

[2] Microbial Chem Res Ctr, Shinagawa Ku, Tokyo 1410021, Japan

[3] Microbial Chem Res Ctr, Hiyoshi Med Chem Res Inst, Nakahara Ku, Kawasaki, Kanagawa 2110035, Japan

来源：

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY | 2005年 / 69卷 / 09期

关键词：

proteasome inhibitor; tyropeptin A derivative;

D O I：

10.1271/bbb.69.1733

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：

Tyropeptin A, a potent proteasome inhibitor, was isolated from the culture broth of Kitasatospora sp. MK993-dF2. We synthesized the derivatives of tyropeptin A to enhance its inhibitory potency. Among the synthesized derivatives, the most potent compound, TP-104, exhibited a 20-fold inhibitory potency enhancement for chymotrypsin-like activity of 20S proteasome compared to tyropeptin A. Additionally, TP-110 specifically inhibited the chymotrypsin-like activity, but did not inhibit the post-glutamyl-peptide hydrolyzing (PGPH) and the trypsin-like activities of 20S proteasome. In vitro TP-110 strongly inhibited the growth of various cell lines.

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页码：1733 / 1742

页数：10

相关论文

共 13 条

[1]

Adams J, 1999, CANCER RES, V59, P2615

[2] 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

[3] DEGRADATION OF NUCLEAR ONCOPROTEINS BY THE UBIQUITIN SYSTEM INVITRO [J].

CIECHANOVER, A ;

DIGIUSEPPE, JA ;

BERCOVICH, B ;

ORIAN, A ;

RICHTER, JD ;

SCHWARTZ, AL ;

BRODEUR, GM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (01) :139-143

[4] Structure and functions of the 20S and 26S proteasomes [J].

Coux, O ;

Tanaka, K ;

Goldberg, AL .

ANNUAL REVIEW OF BIOCHEMISTRY, 1996, 65 :801-847

[5] Ubiquitination of p53 and p21 is differentially affected by ionizing and UV radiation [J].

Maki, CG ;

Howley, PM .

MOLECULAR AND CELLULAR BIOLOGY, 1997, 17 (01) :355-363

[6] Structure-based design of derivatives of tyropeptin A as the potent and selective inhibitors of mammalian 20S proteasome [J].

Momose, I ;

Umezawa, Y ;

Hirosawa, S ;

Iinuma, H ;

Ikeda, D .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (07) :1867-1871

[7] Inhibition of proteasome activity by tyropeptin A in PC12 cells [J].

Momose, I ;

Sekizawa, R ;

Iinuma, H ;

Takeuchi, T .

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 2002, 66 (10) :2256-2258

[8] Tyropeptins A and B, new proteasome inhibitors produced by Kitasatospora sp MK993-dF2 -: II.: Structure determination and synthesis [J].

Momose, I ;

Sekizawa, R ;

Hirosawa, S ;

Ikeda, D ;

Naganawa, H ;

Iinuma, H ;

Takeuchi, T .

JOURNAL OF ANTIBIOTICS, 2001, 54 (12) :1004-1012

[9] Tyropeptins A and B, new proteasome inhibitors produced by Kitasatospora sp MK993-dF2 -: I.: Taxonomy, isolation, physico-chemical properties and biological activities [J].

Momose, S ;

Sekizawa, R ;

Hashizume, H ;

Kinoshita, N ;

Homma, Y ;

Hamada, M ;

Iinuma, H ;

Takeuchi, T .

JOURNAL OF ANTIBIOTICS, 2001, 54 (12) :997-1003

[10] ROLE OF THE UBIQUITIN-PROTEASOME PATHWAY IN REGULATING ABUNDANCE OF THE CYCLIN-DEPENDENT KINASE INHIBITOR P27 [J].

PAGANO, M ;

TAM, SW ;

THEODORAS, AM ;

BEERROMERO, P ;

DELSAL, G ;

CHAU, V ;

YEW, PR ;

DRAETTA, GF ;

ROLFE, M .

SCIENCE, 1995, 269 (5224) :682-685