Modulation of human estrogen receptor α activity by multivalent estradiol-peptidomimetic conjugates

被引：8
作者：
Holub, Justin M. [1 ]
Garabedian, Michael J. [2 ]
Kirshenbaum, Kent [1 ]
机构：
[1] NYU, Dept Chem, New York, NY 10003 USA
[2] NYU, Langone Sch Med, Dept Microbiol, New York, NY 10016 USA
来源：
MOLECULAR BIOSYSTEMS | 2011年 / 7卷 / 02期
关键词：
PEPTOIDS; MECHANISMS; PEPTIDE; CLICK; BINDING; BETA; GENE; EXPRESSION; PATHWAYS; LIGANDS;
D O I：
10.1039/c0mb00189a
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：
Estradiol-peptidomimetic conjugates (EPCs) are linear, sequence-specific peptoid oligomers that site-specifically display multiple copies of 17 beta-estradiol (E2), a ligand for the human estrogen receptor alpha (hER alpha). We evaluate the ability of multivalent EPCs to activate hER alpha-mediated transcription. EPCs activated the hERa in both a length-and valence-dependent manner, with the highest levels of activation generated by divalent peptoid 6-mers, divalent 18-mers, and trivalent 9-mers. Hexavalent EPCs did not activate hER alpha, but instead blocked E2-mediated hER alpha activation. The physicochemical features of EPCs can be precisely tuned, which may allow the generation of a library of chemical tools for modulating specific effects of estrogens.
引用
收藏
页码：337 / 345
页数：9
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