Probing the water coordination of protein-targeted MRI contrast agents by pulsed ENDOR spectroscopy.
A novel methodology based on electron-nuclear double resonance (ENDOR) spectroscopy is used for the direct determination of the water coordination number (q) of gadolinium-based magnetic resonance imaging (MRI) contrast agents. Proton ENDOR spectra can be obtained at approximately physiological concentrations for metal complexes in frozen aqueous solutions either in the presence or absence of protein targets. It is shown that, depending on the structure of the co-ligand, the water hydration number of a complex in aqueous solution can be significantly different to when the complex is noncovalently bound to a protein. From the ENDOR spectra of the exchangeable protons, precise information on the metal-proton distance can be derived as well. These essential parameters directly correlate with the efficacy of MRI contrast agents and should therefore aid the development of novel, highly efficient compounds targeted to various proteins.
Zech
Stephan G
SG
EPIX Pharmaceuticals, Inc., 67 Rogers Street, Cambridge, MA 02142, USA. szech@epixpharma.com
Sun
Wei-Chuan
WC
Jacques
Vincent
V
Caravan
Peter
P
Astashkin
Andrei V
AV
Raitsimring
Arnold M
AM
D003287:Contrast Media / Q000737:chemistry*; D004578:Electron Spin Resonance Spectroscopy; D005682:Gadolinium / Q000737:chemistry*; D008279:Magnetic Resonance Imaging; D015394:Molecular Structure; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D012996:Solutions; D014867:Water / Q000737:chemistry*
D003287:Contrast Media; D011506:Proteins; D012996:Solutions; D014867:Water; D005682:Gadolinium