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
收藏
页码：2283 / 2288
页数：6
相关论文
共 24 条
  • [1] A MAMMALIAN PROTEIN TARGETED BY G1-ARRESTING RAPAMYCIN-RECEPTOR COMPLEX
    BROWN, EJ
    ALBERS, MW
    SHIN, TB
    ICHIKAWA, K
    KEITH, CT
    LANE, WS
    SCHREIBER, SL
    [J]. NATURE, 1994, 369 (6483) : 756 - 758
  • [2] ADVANTAGEOUS APPLICATIONS OF AZABENZOTRIAZOLE (TRIAZOLOPYRIDINE)-BASED COUPLING REAGENTS TO SOLID-PHASE PEPTIDE-SYNTHESIS
    CARPINO, LA
    EL-FAHAM, A
    MINOR, CA
    ALBERICIO, F
    [J]. JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1994, (02) : 201 - 203
  • [3] 1-HYDROXY-7-AZABENZOTRIAZOLE - AN EFFICIENT PEPTIDE COUPLING ADDITIVE
    CARPINO, LA
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (10) : 4397 - 4398
  • [4] FEHRENTZ JA, 1983, SYNTHESIS-STUTTGART, P676
  • [5] INHIBITION OF PROTEASOME ACTIVITIES AND SUBUNIT-SPECIFIC AMINO-TERMINAL THREONINE MODIFICATION BY LACTACYSTIN
    FENTEANY, G
    STANDAERT, RF
    LANE, WS
    CHOI, S
    COREY, EJ
    SCHREIBER, SL
    [J]. SCIENCE, 1995, 268 (5211) : 726 - 731
  • [6] SOLID-PHASE PEPTIDE-SYNTHESIS UTILIZING 9-FLUORENYLMETHOXYCARBONYL AMINO-ACIDS
    FIELDS, GB
    NOBLE, RL
    [J]. INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH, 1990, 35 (03): : 161 - 214
  • [7] Grant G. A., 1992, SYNTHETIC PEPTIDES U
  • [8] EPOXOMICIN, A NEW ANTITUMOR AGENT OF MICROBIAL ORIGIN
    HANADA, M
    SUGAWARA, K
    KANETA, K
    TODA, S
    NISHIYAMA, Y
    TOMITA, K
    YAMAMOTO, H
    KONISHI, M
    OKI, T
    [J]. JOURNAL OF ANTIBIOTICS, 1992, 45 (11) : 1746 - 1752
  • [9] Proteasomes: Destruction as a programme
    Hilt, W
    Wolf, DH
    [J]. TRENDS IN BIOCHEMICAL SCIENCES, 1996, 21 (03) : 96 - 102
  • [10] A TOTAL SYNTHESIS OF 6,7-DIHYDROEPONEMYCIN AND DETERMINATION OF STEREOCHEMISTRY OF THE EPOXIDE RING
    HOSHI, H
    OHNUMA, T
    ABURAKI, S
    KONISHI, M
    OKI, T
    [J]. TETRAHEDRON LETTERS, 1993, 34 (06) : 1047 - 1050
123