Use of surface plasmon resonance biosensor technology as a possible alternative to detect differences in binding of enantiomeric drug compounds to immobilized albumins.
Use of surface plasmon resonance biosensor technology as a possible alternative to detect differences in binding of enantiomeric drug compounds to immobilized albumins.
复制标题
使用表面等离子共振生物传感器技术作为可能的替代方案来检测对映体药物化合物与固定化白蛋白结合的差异。
DOI：
10.1016/s0956-5663(02)00139-2
复制
发表时间：
2003
影响因子：
12.6
通讯作者：
A. Breau
中科院分区：
文献类型：
--
作者：
Ateeq Ahmad;A. Ramakrishnan;M. McLean;A. Breau
使用生物传感器监测生物分子和药物化合物之间的真实的时间相互作用与现有的检测方法相比具有许多优点，主要的优点是消除了放射性标记和快速筛选。我们还可以获得有关动力学参数的信息，这些值可以作为密切相关的药物化合物和对映异构体的结合强度和特征的细微差异的有用指标。使用基于表面等离子体共振（SPR）技术的Biacore 3000生物传感器来评估药物化合物的两种对映体之间的白蛋白结合差异。容易地计算归一化响应（NRU）和亲和常数（KD）。确定了统计参数（如平均归一化响应值、%CV值），以使该技术具有耐用性。对于研究的大多数浓度，获得的%CV值在结合相互作用的预设限度≤25%（FDA药物开发和方法验证方案限度）内。例如，对照药物华法林与人血白蛋白结合的标准化响应的%CV值范围为7.9 - 24.3%。该方法给出了可重复的结果，结果表明对映体与人和大鼠白蛋白的结合模式略有差异。
The use of biosensors for monitoring real time interactions between biomolecules and drug compounds has a lot of advantages over presently existing detection methods, the major ones being the elimination of radio labels and rapid screening. We can also obtain information about the kinetic parameters and these values may serve as useful indicators towards subtle differences in the binding strength and characteristics of closely related drug compounds and enantiomers. The Biacore 3000 biosensor based on the Surface Plasmon Resonance (SPR) technology was used to assess the albumin protein binding differences between two enantiomers of a drug compound. Normalized responses (NRU) and affinity constants (KD) were readily calculated. Statistical parameters like mean normalized responses, %CV values were determined to make the technique robust. The %CV values obtained were within the preset limits of ≤25% (FDA limits for drug development and method validation protocols) for the binding interactions for majority of the concentrations studied. For example, the %CV values for the normalized responses for the binding of the control drug warfarin to human albumin ranged from 7.9 to 24.3%. The method gave reproducible results, and the results indicated slight differences in binding patterns of the enantiomers to human and rat albumin.