The Binding of Flavopiridol to Blood Serum Albumin
The Binding of Flavopiridol to Blood Serum Albumin
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DOI：
10.1002/chir.20925
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发表时间：
2010-01-01
期刊：
影响因子：
2
通讯作者：
Siligardi, Giuliano
中科院分区：
文献类型：
--
作者：
Myatt, Daniel;Johnson, Louise;Siligardi, Giuliano
Flavopiridol是一种有效的细胞周期蛋白依赖性激酶（CDK）抑制剂，目前正在进行抗癌治疗的临床试验。其药物开发的一个限制因素是人体临床试验所需的高剂量。由于flavopiridol与人血清的显著结合，因此建议高剂量是必要的。白蛋白是血清的主要蛋白质组分，并且已被认为是可能的高亲和力结合靶标。我们采用圆二色谱法（以下简称CD）表征了人血清白蛋白与flavopiridol的结合。与人血清白蛋白结合的夫拉匹多在284 nm处具有诊断CD结合峰。在相同的实验条件下，未观察到flavopiridol与牛血清白蛋白的诊断CD结合峰。然而，在较高的白蛋白浓度下，观察到小的CD信号，证实flavopiridol也与牛血清白蛋白结合。Chirality 22：E40-E43，2010. (c)2010 Wiley-Liss，Inc.
Flavopiridol is a potent cyclin-dependant kinase (CDK) inhibitor and is in clinical trials for anticancer treatment. A limiting factor in its drug development has been the high dosage required in human clinical trials. The high dosage is suggested to be necessary because of significant flavopiridol binding to human blood serum. Albumin is the major protein component of blood serum and has been suggested as a likely high affinity binding target. We characterized the binding of human serum albumin to flavopiridol using circular dichroism (hereafter CD). Flavopiridol bound to human serum albumin has a diagnostic CD binding peak at 284 nm. The diagnostic CD binding peak was unobservable for flavopiridol with bovine serum albumin, using the same experimental conditions. However, under higher albumin concentrations a small CD signal is observed confirming, flavopiridol binds to bovine serum albumin as well. Chirality 22:E40-E43, 2010. (c) 2010 Wiley-Liss, Inc.