Albumin-binding PARACEST agents
Albumin-binding PARACEST agents
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DOI：
10.1007/s00775-007-0240-z
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发表时间：
2007-08-01
影响因子：
3
通讯作者：
Sherry, A. Dean
中科院分区：
文献类型：
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作者：
Ali, M. Meser;Woods, Mark;Sherry, A. Dean
合成了2个和4个O-苄基-L-丝氨酸酰胺取代的1，4，7，10-四氮杂环十二烷-1，4，7，10-四乙酸四酰胺衍生物的稀土配合物（Eu ~（3+）、Gd ~（3+）和Yb ~（3+）），研究了它们在人血清白蛋白（HSA）存在和不存在下的化学交换饱和转移（CEST）和弛豫性质。Eu 2和Eu 3都显示出来自单个缓慢交换的Eu 3+结合水分子的显著CEST效应，使得这些PARACEST络合物潜在地可用作血管MRI剂。Yb 2也显示出可检测的CEST效应，从Yb 3+结合的水质子和可交换的NH酰胺质子，使其潜在的有用的血管pH传感器。荧光置换研究报告分子表明，Gd 2和Gd 3取代dansylsarcosine从网站II的HSA的抑制常数分别为32和96 μ M，但无论是复杂的显着取代华法林从网站I。水质子弛豫增强135和171%的Gd 2和Gd 3的HSA，分别在298 K和pH 7.4的结合后观察到。
Lanthanide complexes (Eu3+, Gd3+ and Yb3+ of two different 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid tetraamide derivatives containing two (2) and four (3) O-benzyl-L-serine amide substituents were synthesized and their chemical exchange saturation transfer (CEST) and relaxometric properties were examined in the presence and absence of human serum albumin (HSA). Both Eu2 and Eu3 display a significant CEST effect from a single slowly exchanging Eu3+-bound water molecule, making these PARACEST complexes potentially useful as vascular MRI agents. Yb2 also showed a detectable CEST effect from both the Yb3+-bound water protons and the exchangeable NH amide protons, making it potentially useful as a vascular pH sensor. Fluorescence displacement studies using reporter molecules indicate that both Gd2 and Gd3 displace dansylsarcosine from site II of HSA with inhibition constants of 32 and 96 mu M, respectively, but neither complex significantly displaces warfarin from site I. Water proton relaxation enhancements of 135 and 171% were observed upon binding of Gd2 and Gd3 to HSA, respectively, at 298 K and pH 7.4.