This research was supported in part by grants from the National Institutes of Health (CA-115531, DK-058398, EB-04285, and RR-02584), the Department of Defense Breast Cancer Research Program (Idea grant W81XWH-05-1-0223), and the Robert A. Welch Foundation (AT-584).
Journal of Biological Inorganic Chemistry
Contrast media (Diagnostic imaging), Magnetic resonance imaging, Serum albumin, Ligand binding (Biochemistry)
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 μM, 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.
Ali, M. M., Woods, M., Suh, E. H., Kovacs, Z., Tircsó, G., Zhao, P., ... & Sherry, A. D. (2007). Albumin-binding PARACEST agents. JBIC Journal of Biological Inorganic Chemistry, 12(6), 855-865.