Ali M Meser, Woods Mark, Suh Eul Hyun, Kovacs Zoltan, Tircsó Gyula, Zhao Piyu, Kodibagkar Vikram D, Sherry A Dean
Department of Chemistry, University of Texas at Dallas, P.O. Box 830688, Richardson, TX 75083-0688, USA.
J Biol Inorg Chem. 2007 Aug;12(6):855-65. doi: 10.1007/s00775-007-0240-z. Epub 2007 May 30.
Lanthanide complexes (Eu(3+), Gd(3+) and Yb(3+)) 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 Eu(3+)-bound water molecule, making these PARACEST complexes potentially useful as vascular MRI agents. Yb2 also showed a detectable CEST effect from both the Yb(3+)-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 microM, 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.
合成了两种不同的含两个（2）和四个（3）O-苄基-L-丝氨酸酰胺取代基的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镧系元素配合物（铕（3+）、钆（3+）和镱（3+）），并在有和无人血清白蛋白（HSA）存在的情况下研究了它们的化学交换饱和转移（CEST）和弛豫特性。Eu2和Eu3均从单个缓慢交换的Eu（3+）结合水分子显示出显著的CEST效应，使得这些PARACEST配合物有潜力用作血管磁共振成像剂。Yb2也从Yb（3+）结合的水质子和可交换的NH酰胺质子显示出可检测的CEST效应，使其有潜力用作血管pH传感器。使用报告分子的荧光位移研究表明，Gd2和Gd3分别以32和96μM的抑制常数从HSA的位点II取代丹磺酰肌氨酸，但两种配合物均未从位点I显著取代华法林。在298K和pH 7.4条件下，Gd2和Gd3与HSA结合时分别观察到水质子弛豫增强135%和171%。
