Gd(III) complexes as contrast agents for magnetic resonance imaging: A proton relaxation enhancement study of the interaction with human serum albumin
Gd(III) complexes as contrast agents for magnetic resonance imaging: A proton relaxation enhancement study of the interaction with human serum albumin
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DOI：
10.1007/s007750050059
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发表时间：
1996-08-01
影响因子：
3
通讯作者：
Terreno, E
中科院分区：
文献类型：
--
作者：
Aime, S;Botta, M;Terreno, E
通过测定人血清白蛋白(HSA)及其水溶液的溶剂质子弛豫速率，研究了含疏水苯氧甲基(BOM)取代基的DOTA类Gd(III)配合物与人血清白蛋白(HSA)之间的非共价相互作用。与人血清白蛋白结合的结合常数(K-A)与络合物表面的疏水取代基数直接相关。此外，根据K-A随温度的变化关系，得到了增量H度和增量S度的估计值。用竞争探针华法林和布洛芬进行的分析表明，这些复合体通过位于蛋白质IIA和IIIA亚域的两个几乎相同的结合部位与HSA相互作用。对于含有两个和三个疏水取代基的络合物，在20 MHz下测量到了由缓慢滚动的顺磁加合物的形成所促进的强烈的弛豫增强作用。与后者的大分子加合物的驰豫系数为53.2+/-0.7 mm(-1)S(-1)，这是迄今为止报道的最高的Gd(III)配合物。顺磁与人血清白蛋白加合物的弛豫度与温度的关系表明，与顺磁中心偶极相互作用的水分子具有较长的交换寿命。这可能与络合物与人血清白蛋白疏水相互作用时形成笼状二配位球状排列的水分子有关。除了影响配位水分子的解离途径外，这种水排列方式本身也可能显著地提高整体溶剂的松弛速率。
The non-covalent interaction between human serum albumin (HSA) and DOTA-like Gd(III) complexes containing hydrophobic benzyloxymethyl (BOM) substituents has been thoroughly investigated by measuring the solvent proton relaxation rates of their aqueous solutions. The binding association constants (K-A) to HSA are directly related to the number of hydrophobic substituents present on the surface of the complexes. Furthermore, an estimation of Delta H degrees and Delta S degrees has been obtained by the temperature dependence of K-A. Assays performed with the competitor probes warfarin and ibuprofen established that the complexes interact with HSA through two nearly equivalent binding sites located in the subdomains IIA and IIIA of the protein. Strong relaxation enhancements, promoted by the formation of slowly tumbling paramagnetic adducts, have been measured at 20 MHz for complexes containing two and three hydrophobic substituents. The macromolecular adduct with the latter species has a relaxivity of 53.2 +/- 0.7 mM(-1) s(-1), which represents the highest value so far reported for a Gd(III) complex. The temperature dependence of the relaxivity for the paramagnetic adducts with HSA indicates long exchange lifetimes for the water molecules dipolarly interacting with the paramagnetic centre. This is likely to be related to the formation, upon hydrophobic interaction of the complexes with HSA, of a clathrate-like, second-coordination-sphere arrangement of water molecules. Besides affecting the dissociative pathway of the coordinated water molecule, this water arrangement may itself significantly contribute to enhancement of the bulk solvent relaxation rate.