Total synthesis of the potent proteasome inhibitor epoxomicin: A useful tool for understanding proteasome biology

被引：158

作者：

Sin, N

Kim, KB

Elofsson, M

Meng, LH

Auth, H

Kwok, BHB

Crews, CM ^{[1
]}

机构：

[1] Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06520 USA

[2] Yale Univ, Dept Pharmacol, New Haven, CT 06520 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1999年 / 9卷 / 15期

关键词：

D O I：

10.1016/S0960-894X(99)00376-5

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Epoxomicin (1), a peptide alpha',beta'-epoxyketone isolated from the actinomycete strain No.Q996-17, possesses potent in vivo anti-tumor and anti-inflammatory activities. In this paper, we report the first syntheses of epoxomicin, [H-3]-epoxomicin, and a biotinylated epoxomicin analog as well as the absolute configuration of the epoxide stereocenter. The natural product and derivatives have permitted the first identification of the proteasome as the specific cellular target of epoxomicin. (C) 1999 Elsevier Science Ltd. All rights reserved.

引用

页码：2283 / 2288

页数：6

共 24 条

[11] Proteasome inhibitors: valuable new tools for cell biologists
Lee, DH
Goldberg, AL
[J]. TRENDS IN CELL BIOLOGY, 1998, 8 (10) : 397 - 403
[12] CALCINEURIN IS A COMMON TARGET OF CYCLOPHILIN-CYCLOSPORINE-A AND FKBP-FK506 COMPLEXES
LIU, J
FARMER, JD
LANE, WS
FRIEDMAN, J
WEISSMAN, I
SCHREIBER, SL
[J]. CELL, 1991, 66 (04) : 807 - 815
[13] MENG L, 1999, IN P0RESS P NATL ACA
[14] Meng LH, 1999, CANCER RES, V59, P2798
[15] Design and synthesis of dipeptidyl α′,β′-epoxy ketones, potent irreversible inhibitors of the cysteine protease cruzain
Roush, WR
González, FV
McKerrow, JH
Hansell, E
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1998, 8 (19) : 2809 - 2812
[16] SCHMIDT U, 1994, SYNTHESIS-STUTTGART, P300
[17] THE SYNTHESIS OF EPONEMYCIN
SCHMIDT, U
SCHMIDT, J
[J]. JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1992, (07) : 529 - 530
[18] Chemical genetics resulting from a passion for synthetic organic chemistry
Schreiber, SL
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 1998, 6 (08) : 1127 - 1152
[19] The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2
Sin, N
Meng, LH
Wang, MQW
Wen, JJ
Bornmann, WG
Crews, CM
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (12) : 6099 - 6103
[20] Eponemycin analogues: Syntheses and use as probes of angiogenesis
Sin, N
Meng, LH
Auth, H
Crews, CM
[J]. BIOORGANIC & MEDICINAL CHEMISTRY, 1998, 6 (08) : 1209 - 1217

← 1 2 3 →