异三齿羟基吡啶酸钆配合物：合成、弛豫性能、水交换动力学及与人血清白蛋白的结合

Hetero-tripodal hydroxypyridonate gadolinium complexes: syntheses, relaxometric properties, water exchange dynamics, and human serum albumin binding.

作者信息

Thompson Marlon K, Doble Dan M J, Tso Luke S, Barra Serena, Botta Mauro, Aime Silvio, Raymond Kenneth N

机构信息

Department of Chemistry, University of California, Berkeley, California 94720, USA.

出版信息

Inorg Chem. 2004 Dec 27;43(26):8577-86. doi: 10.1021/ic048607u.

DOI:10.1021/ic048607u

PMID:15606209

Abstract

The synthesis and relaxometric properties of hetero-tripodal hydroxypyridonate-terephthalamide gadolinium (Gd(3+)) chelates with differing structural features for probing human serum albumin (HSA) interactions are reported. The Gd(3+) 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).

摘要

本文报道了具有不同结构特征的异三齿羟基吡啶酮-对苯二甲酰胺钆（Gd(3+)）螯合物的合成及其弛豫特性，用于探究其与人血清白蛋白（HSA）的相互作用。Gd(3+)配合物分为两个系列。第一个系列（3-5）的特征是苄基衍生物连接到羟基吡啶酮（HOPO）部分。第二个系列的配合物（6-10）的共同特征是聚乙二醇（PEG）连接到对苯二甲酰胺（TAM）部分且未苄基化。配合物的水交换处于快速交换区域，速率（k(ex)）在0.45-1.11×10(8) s(-1)范围内。这些配合物与HSA有适度的相互作用，缔合常数（K(A)）在0.7-8.6×10(3) M(-1)范围内。蛋白质结合导致质子弛豫率从7.7-10.4 mM(-1) s(-1)（r(1p)）提高到15-29 mM(-1) s(-1)（r(1p)(b)）。得出的结论是，配合物与HSA的相互作用：（i）因苄基的存在而增强；（ii）是由熵驱动的；（iii）导致水合数（q）降低。