Isolation and structure elucidation of chlorofusin, a novel p53-MDM2 antagonist from a Fusarium sp.

被引:145
作者
Duncan, SJ [1 ]
Grüschow, S [1 ]
Williams, DH [1 ]
McNicholas, C [1 ]
Purewal, R [1 ]
Hajek, M [1 ]
Gerlitz, M [1 ]
Martin, S [1 ]
Wrigley, SK [1 ]
Moore, M [1 ]
机构
[1] Univ Cambridge, Cambridge Ctr Mol Recognit, Chem Lab, Cambridge CB2 1EW, England
关键词
D O I
10.1021/ja002940p
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Wild-type p53 plays a crucial role in the prevention of cancer. Since dysfunction of p53 can be caused by increased levels of the protein MDM2, small molecules which antagonize the interaction between these two-proteins have-potential in cancer therapy. The discovery and structure determination of a fungal metabolite, chlorofusin, which antagonizes the p53/MDM2 interaction are reported.
引用
收藏
页码:554 / 560
页数:7
相关论文
共 16 条
  • [11] ONCOPROTEIN MDM2 CONCEALS THE ACTIVATION DOMAIN OF TUMOR SUPPRESSOR-P53
    OLINER, JD
    PIETENPOL, JA
    THIAGALINGAM, S
    GVURIS, J
    KINZLER, KW
    VOGELSTEIN, B
    [J]. NATURE, 1993, 362 (6423) : 857 - 860
  • [12] BETA-BULGE - COMMON SMALL UNIT OF NONREPETITIVE PROTEIN-STRUCTURE
    RICHARDSON, JS
    GETZOFF, ED
    RICHARDSON, DC
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1978, 75 (06) : 2574 - 2578
  • [13] One-dimensional NOE experiments using pulsed field gradients
    Stott, K
    Keeler, J
    Van, QN
    Shaka, AJ
    [J]. JOURNAL OF MAGNETIC RESONANCE, 1997, 125 (02) : 302 - 324
  • [14] WRIGLEY S, 1997, PHYTOCHEMICAL DIVERS
  • [15] THE P53 MDM-2 AUTOREGULATORY FEEDBACK LOOP
    WU, XW
    BAYLE, JH
    OLSON, D
    LEVINE, AJ
    [J]. GENES & DEVELOPMENT, 1993, 7 (7A) : 1126 - 1132
  • [16] Wuthrich K., 1986, NMR PROTEINS NUCL AC, DOI DOI 10.1051/EPN/19861701011