Hetero-tripodal hydroxypyridonate gadolinium complexes: Syntheses, relaxometric properties, water exchange dynamics, and human serum albumin binding
Hetero-tripodal hydroxypyridonate gadolinium complexes: Syntheses, relaxometric properties, water exchange dynamics, and human serum albumin binding
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DOI：
10.1021/ic048607u
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发表时间：
2004-12-27
影响因子：
4.6
通讯作者：
Raymond, KN
中科院分区：
文献类型：
--
作者：
Thompson, MK;Doble, DMJ;Raymond, KN
报道了用于探测人血清白蛋白(HSA)相互作用的具有不同结构特征的杂三脚羟基吡啶-对苯二甲酰胺(Gd3+)络合物的合成及其弛豫性能。Gd3+络合物分为两个系列。第一系列(3-5)的特征是连接到羟基吡啶酮酸酯(HOPO)部分的苯基衍生物。第二系列络合物(6-10)具有聚乙二醇键接到对苯二甲酰胺()部分的共同特征，并且是非苄化的。络合物的水交换处于快速交换区域，交换速率k(Ex)在0.45-1.11×10~(-8)S(-1)范围内。配合物与人血清白蛋白有中等的相互作用，其缔合常数(K-A‘s)在0.7-8.6×10(3)M-1范围内。蛋白质结合使质子弛豫度从7.710.4 mm(-1)S(-1)(r(1p))增加到15-29 mm(-1)S(-1)(r(1p)(B))。结果表明，该络合物与人血清白蛋白(I)的相互作用因苄基的存在而增强，(II)是以熵驱动的，(III)导致较低的水化数(Q)。
The synthesis and relaxometric properties of hetero-tripodal hydroxypyridonate-terephthalamide gadolinium (Gd3+) chelates with differing structural features for probing human serum albumin (HSA) interactions are reported. The Gd3+ complexes are divided into two series. The first series (3-5) features a benzyl derivative connected to the hydroxypyridonate (HOPO) moiety. The second series of complexes (6-10) has the common feature of a poly(ethylene glycol) (PEG) attached to the terephthalamide (TAM) moiety and is nonbenzylated. The water exchange of the complexes is in the fast exchange regime with rates (k(ex)) in the range 0.45-1.11 x 10(8) s(-1). The complexes have a moderate interaction with HSA with association constants (K-A's) in the range 0.7-8.6 x 10(3) M-1. Protein binding results in an enhancement in proton relaxivity from 7.7-10.4 mM(-1) s(-1) (r(1p)) to 15-29 mM(-1) s(-1) (r(1p)(b)). It is concluded that the interaction of the complexes with HSA (i) is enhanced by the presence of benzyl groups, (ii) is entropically driven, and (iii) results in a lower hydration number (q).