Microenviromental Analysis of Drug Binding Site on Albumin by Point-mutation and Using Probe

利用点突变和探针对白蛋白药物结合位点进行微环境分析

• 批准号: 06672146
• 负责人: OTAGIRI Masaki
• 金额: $ 1.54万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06672146/
• 关键词: Albumin; Drug Binding Site; Probe; Point-mutation; Microenvironmental Analysis; Species Difference; 蛋白結合; プローブ法; 微環境解析; 薬物結合サイト; N-B転移

It is well-known that human serum albumin (HSA) has three specific binding sites for drugs, called site I,site II and site III.In addition, recent studies by X-ray crystal analysis indicated that the principal drug binding sites are located in subdomains IIA and IIIA.However, the drug binding sites on serum albumin for experimental animals such as rat, rabbit and dog have not yet been determined. Therefore, this investigation has been undertaken to study the characterization of these drug binding sites in the abovementioned animals. All the albumin examined have found to have at least two specific drug binding sites similar to human albumin using fluorescent probes. Further, using the different binding models assuming independent, competitive and anticooperative binding, these hypothesis were supported. The site I or site II on the albumin molecules seemed to be wide area consisting of subsites. However, unfortunately, we could not determine the microenvironmental analysis using the point-mutagenic techniques.

众所周知，人血清白蛋白（HSA）具有3个药物特异性结合位点，分别为位点I、位点II和位点III，近年来的X射线晶体分析表明，主要的药物结合位点位于IIA和IIIA亚区，但大鼠、兔和狗等实验动物血清白蛋白的药物结合位点尚未确定。因此，本研究旨在研究上述动物中这些药物结合位点的表征。所有的白蛋白检测发现至少有两个特异性药物结合位点类似于人白蛋白使用荧光探针。此外，使用不同的结合模型假设独立，竞争和反合作的结合，这些假设得到了支持。白蛋白分子上的位点I或位点II似乎是由亚位点组成的宽区域。然而，不幸的是，我们不能确定微环境分析使用点诱变技术。

项目成果

Keishi Yamasaki, Masaki Otagiri et al.: "Charactarization of Site I on Human Serum Albumin : Concept about the Structure of a Drug Binding Site" Biochemical Biophysica Acta. 1278, (in press). (1996)

Keishi Yamasaki、Masaki Otagiri 等人：“人血清白蛋白位点 I 的表征：药物结合位点结构的概念”《生物化学生物物理学学报》。

Norito Takamura, Masaki Otagiri et al.: "Mode of Interaction of Loop Diuretics with Human Serum Albumin and Charactarization of Binding Site" Phamaceutical Research. (in press). (1996)

Norito Takamura、Masaki Otagiri 等人：“袢利尿剂与人血清白蛋白的相互作用模式和结合位点的表征”药物研究。

H.Vorum,小田切優樹(他4名): "Calcium Ion Binding to Clinically Relevant Chemical Modifications of Human Serum Albumin" Clinical Chemistry. 41. 1654-1661 (1995)

H. Vorum、Yuki Odagiri（以及其他 4 人）：“钙离子与人血清白蛋白的临床相关化学修饰的结合”《临床化学》41. 1654-1661 (1995)。

山崎啓之,小田切優樹(他2名): "Characterization of Site I on Human Serum Albumin : Concept about the Structure of a Drug Binding Site" Biochemical Biophysica Acta. 1278. (1996)

Hiroyuki Yamazaki、Yuki Odagiri（以及其他 2 人）：“人血清白蛋白位点 I 的表征：药物结合位点结构的概念”《生物化学生物物理学学报》1278。（1996 年）

高村徳人,小田切優樹(他5名): "Mode of Interaction of Loop Diuretics with Human Serum Albumin and Characterization of Binding Site" Pharmaceutical Research. (1996)

Norito Takamura、Yuki Odagiri（以及其他 5 人）：“袢利尿剂与人血清白蛋白的相互作用模式和结合位点的表征”药物研究 (1996)。