A polyaromatic receptor with high androgen affinity
A polyaromatic receptor with high androgen affinity
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DOI：
10.1126/sciadv.aav3179
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发表时间：
2019-04
期刊：
影响因子：
13.6
通讯作者：
Masahiro Yamashina;T. Tsutsui;Y. Sei;M. Akita;M. Yoshizawa
中科院分区：
文献类型：
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作者：
Masahiro Yamashina;T. Tsutsui;Y. Sei;M. Akita;M. Yoshizawa
雄激素生物受体的合成模型在其多芳香腔中严格区分雄性激素和雌性激素。生物受体区分和结合类固醇性激素，如雄激素型、孕激素型和雌激素型，具有高选择性。迄今为止，人工分子受体还不能区分这两类生物底物。在这里，我们报告了人工多芳香受体优先结合单分子雄激素，称为“雄性”激素（用m表示），而不是孕激素和雌激素，称为“雌性”激素（用f表示），在水中。竞争性实验确定了合成受体对多种性激素的结合选择性为睾酮(m) >雄酮(m) >>孕酮(f) > β-雌二醇(f) >孕烯醇酮(f) >雌三醇(f)。这些结合是由疏水效应驱动的，所观察到的选择性来自于半刚性多芳腔中的多个CH-π接触和氢键相互作用。此外，使用含有荧光染料的受体在水中证明了雄激素的微摩尔荧光检测。
A synthetic model of androgen bioreceptors strictly discriminates male hormones from female ones in its polyaromatic cavity. Biological receptors distinguish and bind steroid sex hormones, e.g., androgen-, progestogen-, and estrogen-type hormones, with high selectivity. To date, artificial molecular receptors have been unable to discriminate between these classes of biosubstrates. Here, we report that an artificial polyaromatic receptor preferentially binds a single molecule of androgenic hormones, known as “male” hormones (indicated with m), over progestogens and estrogens, known as “female” hormones (indicated with f), in water. Competitive experiments established the binding selectivity of the synthetic receptor for various sex hormones to be testosterone (m) > androsterone (m) >> progesterone (f) > β-estradiol (f) > pregnenolone (f) > estriol (f). These bindings are driven by the hydrophobic effect, and the observed selectivity arises from multiple CH-π contacts and hydrogen-bonding interactions in the semirigid polyaromatic cavity. Furthermore, micromolar fluorescence detection of androgen was demonstrated using the receptor containing a fluorescent dye in water.