阿片样物质在人类血清白蛋白结合位点。
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周R, Perez-Aguilar JM,孟Q, Saven詹,刘R
阿片样物质在人类血清白蛋白结合位点。
1月Anesth。2012; 114 (1): 122 - 8。doi: 10.1213 / ANE.0b013e318232e922。Epub 2011年10月24日。
- PubMed ID
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22025496 (在PubMed]
- 文摘
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背景:人血清白蛋白(HSA)是阿片类药物的一个重要载体。然而,结合位点的位置尚不清楚。opioid-HSA交互特征在目前的研究中,我们使用多个生物化学和生物物理技术来揭示:(a)结合位点的位置(年代);(b)是否纳洛酮的结合位点与吗啡;和(c)是否阿片受体激动剂分享他们的结合位点(s)与一般的麻醉剂。方法:洗脱色谱法确定全球交互和色氨酸固有荧光与HSA确定阿片类药物的局部相互作用。竞争研究使用等温滴定量热法被用来确定结合位点的重叠(s)在阿片受体激动剂,对手,和一般的麻醉剂。自动对接计算被用来预测可能的结合位点和评估发现解决方案的研究。结果:对于固定化HSA的洗脱色谱法,纳洛酮的保留时间,吗啡、芬太尼持续但短于异丙酚。纳洛酮的抑制色氨酸荧光不受吗啡或芬太尼。 The calorimetric heat profiles of propofol and halothane interaction with HSA were changed significantly, but not equally by morphine, naloxone, or fentanyl. Consistent with direct binding studies, docking results demonstrated that opioids share sites with general anesthetics; a distinct binding site for naloxone was revealed near the sole tryptophan in HSA that is not shared with morphine. CONCLUSIONS: The interaction of opioids with HSA is weak in comparison with propofol. Naloxone has a distinct binding site in HSA not shared with opioid agonists. Opioids share binding sites with general anesthetics in HSA.