Jenkins B G, Armstrong E, Lauffer R B
Department of Radiology, Massachusetts General Hospital, Boston.
Magn Reson Med. 1991 Jan;17(1):164-78. doi: 10.1002/mrm.1910170120.
Binding of potential blood pool and hepatobiliary paramagnetic iron(III) contrast agents, rac- and meso-Fe(5-Br-EHPG)- (iron(III) N,N'-ethylenebis [(5-bromo-2-hydroxyphenyl)glycinate]) and Fe(5-Br-HBED)- (iron(III) N,N'-bis-(5-bromo-2-hydroxybenzyl)ethylenediaminediacetic acid) to human serum albumin (HSA) has been studied using the proton relaxation enhancement (PRE) effect on solvent protons. These chelates bind avidly to multiple sites on HSA with binding constants on the order of 10(4) to 10(5) M-1. Interestingly, binding results in a decrease in the diamagnetic component of the water relaxivity due to HSA, while the expected enhancement of the paramagnetic component of water proton relaxation rates occurs due to the increase in the rotational correlation times of the protein-bound agents. These relaxation enhancements are variable, depending upon the site on the protein to which these chelates are bound, and can be as high as approximately 7 mM-1 s-1 at 5 degrees C and approximately 5 mM-1 s-1 at 37 degrees C at 20 MHz (enhancements of approximately 2-5). Change of temperature from 5 to 37 degrees C also appears to switch the relative affinities of these chelates for their primary and secondary binding sites. It is found that the important HSA binding site for the heme breakdown product, bilirubin-IX alpha, is a target for these agents and is the site of highest relaxivity for all the agents.
利用对溶剂质子的质子弛豫增强（PRE）效应，研究了潜在的血池和肝胆顺磁性铁（III）造影剂，外消旋和内消旋-Fe(5-Br-EHPG)-（铁（III）N,N'-亚乙基双[(5-溴-2-羟基苯基)甘氨酸酯]）和Fe(5-Br-HBED)-（铁（III）N,N'-双-(5-溴-2-羟基苄基)乙二胺二乙酸）与人血清白蛋白（HSA）的结合。这些螯合物与HSA上的多个位点紧密结合，结合常数在10⁴至10⁵ M⁻¹范围内。有趣的是，结合导致由于HSA引起的水弛豫率的抗磁成分降低，而由于蛋白质结合剂的旋转相关时间增加，水质子弛豫率的顺磁成分出现预期的增强。这些弛豫增强是可变的，取决于这些螯合物结合到蛋白质上的位点，在20 MHz时，5℃下可高达约7 mM⁻¹ s⁻¹，37℃下约为5 mM⁻¹ s⁻¹（增强约2 - 5倍）。温度从5℃变化到37℃似乎也会改变这些螯合物对其主要和次要结合位点的相对亲和力。发现血红素分解产物胆红素-IXα的重要HSA结合位点是这些试剂的靶标，并且是所有试剂弛豫率最高的位点。
