A β-cyclodextrin "Click Cluster" decorated with seven paramagnetic chelates containing two water exchange sites
A β-cyclodextrin "Click Cluster" decorated with seven paramagnetic chelates containing two water exchange sites
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DOI：
10.1021/bc800200q
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发表时间：
2008-08-01
影响因子：
4.7
通讯作者：
Reineke, Theresa M.
中科院分区：
文献类型：
--
作者：
Bryson, Joshua M.;Chu, Wen-Jang;Reineke, Theresa M.
在高磁场下提供增强弛豫率曲线的新型大分子造影剂的开发具有极大地改善疾病的诊断、理解和治疗的潜力。为此，我们设计了一个单分散顺磁性β-环糊精点击簇装饰有七个顺磁臂。已经产生了新的炔官能化的二亚乙基三胺四乙酸（DTTA）螯合物（6）并将其偶联到全叠氮基-β-环糊精核（7）上以产生前体大分子（8）。在去除保护基并用Gd过滤后，获得最终的顺磁性点击簇Gd 10。在H2O和D2 O中对类似的结构Eu 10进行了发光测量，并表明每个镧系元素平均具有1.8个水交换位点，这对于提高弛豫率和MRI分辨率是重要的。这种离散的顺磁性点击簇产生高弛豫率曲线（在9.4 T下每个分子43.4 mM（-1）s（-1）和每个Gd 3 + 6.2 mM（-1）s（-1）），并且与商业试剂Magenvist（在9.4 T下3.2 mM（-1）s（-1））相比，在人MRI扫描仪上产生增强的对比度。此外，β-环糊精所表现出的有用的包合性质也使其成为通过与受体特异性靶向部分的非共价组装而官能化的优异的主体支架，用于生物分子成像。
The development of novel macromolecular contrast agents that offer enhanced relaxivity profiles at high magnetic fields have the potential to greatly improve the diagnosis, understanding, and treatment of disease. To this end, we have designed a monodiperse paramagnetic beta-cyclodextrin click cluster decorated with seven paramagnetic arms. A novel alkyne-functionalized diethylenetriaminetetraacetic acid (DTTA) chelate (6) has been created and coupled to a per-azido-beta-cyclodextrin core (7) to yield the precursor macromolecule (8). After removal of the protecting groups and fitrating with Gd, the final paramagnetic click cluster, Gd10, was obtained. Luminescence measurements were carried out in H2O and D2O on an analogous structure, Eu10, and indicated that at each lanthanide has an average of 1.8 water exchange sites, which is important for enhancing relaxivity and MRI resolution. This discrete paramagnetic click cluster yields a high relaxivity profile (43.4 mM(-1) s(-1) per molecule and 6.2 mM(-1) s(-1) per Gd3+ at 9.4 T) and enhanced contrast on a human MRI scanner as compared to a commercial agent, Magnevist (3.2 mM(-1) s(-1) at 9.4 T). Moreover, the useful inclusion properties exhibited by beta-cyclodextrin also make this an excellent host scaffold to functionalize via noncovalent assembly with receptor specific targeting moieties for biomolecular imaging.