研究aryloxypropanolamines之间的交互和Asn386螺旋七世的人类5-hydroxytryptamine1A受体。
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Kuipers W,链接R, Standaar PJ, Stoit AR, Van Wijngaarden我,他们R, Ijzerman美联社
研究aryloxypropanolamines之间的交互和Asn386螺旋七世的人类5-hydroxytryptamine1A受体。
51摩尔杂志。1997;(5):889 - 96。
- PubMed ID
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9145928 (在PubMed]
- 文摘
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我们研究了立体选择aryloxypropanolamines之间的相互作用和人类5-hydroxytryptamine1A (5-HT1A)受体。R -和S-enantiomers心得安、penbutolol和阿普洛尔调查的能力结合人类5-HT1A野生型和Asn386Val突变体受体。Asn386似乎作为手性鉴别器。尽管aryloxypropanol对映体显示低亲和力受体突变,S-enantiomers更有亲和力的影响。受体亲和力5-HT1A无关的其他结构的配体并没有降低的突变Asn386缬氨酸。此外,一系列的类似物oxypropanolamine心得安和结构变异的一部分是合成,和野生型和突变5-HT1A Asn386Val受体亲和力测定。羟基和醚氧的原子oxypropanol一半似乎需要绑定在野生型5-HT1A受体。普萘洛尔的羟基可能直接与Asn386交互。醚的氧原子对空间可能是重要原因,但也可以参与与Asn386直接交互。这些发现在赞同与Asn386 aryloxypropanolamines鼠5-HT1A受体的相互作用,我们之前提出。 The loss of affinity for propranolol by the Asn386Val mutation could be regained by replacement of the hydroxyl group of the ligand by a methoxy group. This modification of the propranolol structure has no effect on the affinity of both enantiomers for the wild-type 5-HT1A receptor, which provides an alternative hypothesis for the interaction of Asn386 with the oxypropanol oxygen atoms. According to this novel hypothesis, the oxypropanol oxygen atoms may both act as hydrogen bond acceptors from the NH2 group of Asn386.