Strickland Madeleine, Schwieters Charles D, Göbl Christoph, Opina Ana C L, Strub Marie-Paule, Swenson Rolf E, Vasalatiy Olga, Tjandra Nico
Laboratory of Molecular Biophysics, Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, 20892, USA.
Office of Intramural Research, Center for Information Technology, National Institutes of Health, Bethesda, MD, 20892, USA.
J Biomol NMR. 2016 Oct;66(2):125-139. doi: 10.1007/s10858-016-0061-x. Epub 2016 Sep 22.
Lanthanide complexes based on the DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) cage are commonly used as phase contrast agents in magnetic resonance imaging, but can also be utilized in structural NMR applications due to their ability to induce either paramagnetic relaxation enhancement or a pseudocontact shift (PCS) depending on the choice of the lanthanide. The size and sign of the PCS for any given atom is determined by its coordinates relative to the metal center, and the characteristics of the lanthanide's magnetic susceptibility tensor. Using a polymethylated DOTA tag (Ln-M8-SPy) conjugated to ubiquitin, we calculated the position of the metal center and characterized the susceptibility tensor for a number of lanthanides (dysprosium, thulium, and ytterbium) under a range of pH and temperature conditions. We found that there was a difference in temperature sensitivity for each of the complexes studied, which depended on the size of the lanthanide ion as well as the isomeric state of the cage. Using O-NMR, we confirmed that the temperature sensitivity of the compounds was enhanced by the presence of an apically bound water molecule. Since amide-containing lanthanide complexes are known to be pH sensitive and can be used as probes of physiological pH, we also investigated the effect of pH on the Ln-M8-SPy susceptibility tensor, but we found that the changes in this pH range (5.0-7.4) were not significant.
基于DOTA（1,4,7,10 - 四氮杂环十二烷 - 1,4,7,10 - 四乙酸）笼状结构的镧系配合物通常用作磁共振成像中的相衬剂，但由于它们能够根据镧系元素的选择诱导顺磁弛豫增强或伪接触位移（PCS），因此也可用于结构核磁共振应用。任何给定原子的PCS大小和符号由其相对于金属中心的坐标以及镧系元素的磁化率张量特性决定。通过将多甲基化的DOTA标签（Ln - M8 - SPy）与泛素偶联，我们计算了金属中心的位置，并在一系列pH和温度条件下对多种镧系元素（镝、铥和镱）的磁化率张量进行了表征。我们发现所研究的每种配合物的温度敏感性存在差异，这取决于镧系离子的大小以及笼状结构的异构体状态。使用O - NMR，我们证实了顶端结合的水分子的存在增强了化合物的温度敏感性。由于含酰胺的镧系配合物已知对pH敏感且可作为生理pH的探针，我们还研究了pH对Ln - M8 - SPy磁化率张量的影响，但我们发现在该pH范围（5.0 - 7.4）内的变化并不显著。
