Cyclic pyrrole-imidazole polyamides targeted to the androgen response element

被引：0
|
作者：
Chenoweth, David M. [1 ]
Harki, Daniel A. [1 ]
Phillips, John W. [1 ]
Dose, Christian [1 ]
Dervan, Peter B. [1 ]
机构：
[1] Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, United States
来源：
Journal of the American Chemical Society | 2009年 / 131卷 / 20期
关键词：
Hairpin pyrrole-imidazole (Py-Im) polyamides are a class of cell-permeable DNA-binding small molecules that can disrupt transcription factor-DNA binding and regulate endogenous gene expression. The covalent linkage of antiparallel Py-Im ring pairs with an γ-amino acid turn unit affords the classical hairpin Py-Im polyamide structure. Closing the hairpin with a second turn unit yields a cyclic polyamide; a lesser-studied architecture mainly attributable to synthetic Inaccessibility. We have applied our methodology for solution-phase polyamide synthesis to cyclic polyamides with an Improved high-yield cyclization step. Cyclic 8-ring Py-Im polyamides 1-3 target the DNA sequence 5-WGWWCW-3; which corresponds to the androgen response element (ARE) bound by the androgen receptor transcription factor to modulate gene expression. We find that cyclic Py-Im polyamides 1-3 bind DNA with exceptionally high affinities and regulate the expression of AR target genes In cell culture studies; from which we Infer that the cycle Is cell permeable. © 2009 American Chemical Society;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Journal article (JA)
引用
收藏
页码：7182 / 7188
相关论文
共 50 条
  • [1] Cyclic Pyrrole-Imidazole Polyamides Targeted to the Androgen Response Element
    Chenoweth, David M.
    Harki, Daniel A.
    Phillips, John W.
    Dose, Christian
    Dervan, Peter B.
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2009, 131 (20) : 7182 - 7188
  • [2] Control of Forward/Reverse Orientation Preference of Cyclic Pyrrole-Imidazole Polyamides
    Hirose, Yuki
    Asamitsu, Sefan
    Bando, Toshikazu
    Sugiyama, Hiroshi
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2019, 141 (33) : 13165 - 13170
  • [3] Regulation of gene expression with pyrrole-imidazole polyamides
    Melander, C
    Burnett, R
    Gottesfeld, JM
    JOURNAL OF BIOTECHNOLOGY, 2004, 112 (1-2) : 195 - 220
  • [4] What is the antiviral potential of pyrrole-imidazole polyamides?
    He, Gaofei
    Bashkin, James K.
    FUTURE MEDICINAL CHEMISTRY, 2015, 7 (15) : 1953 - 1955
  • [5] Progress on pyrrole-imidazole polyamides specifically recognizing DNA
    Lu, LP
    Zhu, ML
    Yang, P
    PROGRESS IN CHEMISTRY, 2004, 16 (03) : 422 - 430
  • [6] Efficient synthesis of pyrrole-imidazole polyamides by using the tag
    Shinozaki, Yoshinao
    Watanabe, Takayoshi
    Nagase, Hiroki
    CANCER SCIENCE, 2018, 109 : 1163 - 1163
  • [7] Therapeutic gene regulation using pyrrole-imidazole polyamides
    Yu, Zutao
    Pandian, Ganesh N.
    Hidaka, Takuya
    Sugiyama, Hiroshi
    ADVANCED DRUG DELIVERY REVIEWS, 2019, 147 : 66 - 85
  • [8] Solution-Phase Synthesis of Pyrrole-Imidazole Polyamides
    Chenoweth, David M.
    Harki, Daniel A.
    Dervan, Peter B.
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2009, 131 (20) : 7175 - 7181
  • [9] Recognition of the DNA minor groove by pyrrole-imidazole polyamides
    Dervan, PB
    Edelson, BS
    CURRENT OPINION IN STRUCTURAL BIOLOGY, 2003, 13 (03) : 284 - 299
  • [10] Orientation preferences of pyrrole-imidazole polyamides in the minor groove of DNA
    White, S
    Baird, EE
    Dervan, PB
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (38) : 8756 - 8765
12345