Direct assessment of water exchange on a Gd(III) chelate bound to a protein |
| |
Authors: | É Tóth Fabienne Connac Lothar Helm Kofi Adzamli André E Merbach |
| |
Institution: | (1) Institute of Inorganic and Analytical Chemistry, University of Lausanne, BCH, CH-1015 Lausanne, Switzerland, CH;(2) Imaging Division, Mallinckrodt Inc., 675 McDonnell Blvd., P. O. Box 5840, St. Louis, MO 63134, USA, US |
| |
Abstract: | The Gd(III) complex of 4-pentylbicyclo2.2.2]octane-1-carboxyl-di-l-aspartyl-lysine-derived DTPA, GdL(H2O)]2–, binds to serum albumin in vivo, through hydrophobic interaction. A variable temperature 17O NMR, EPR, and Nuclear Magnetic Relaxation Dispersion (NMRD) study resulted in a water exchange rate of k
298
ex=4.2×106 s–1, and let us conclude that the GdL complex is identical to Gd(DTPA)(H2O)]2– in respect to water exchange and electronic relaxation. The effect of albumin binding on the water exchange rate has been
directly evaluated by 17O NMR. Contrary to expectations, the water exchange rate on GdL does not decrease considerably when bound to bovine serum
albumin (BSA); the lowest limit can be given as k
ex, GdL-BSA=k
ex, GdL / 2. In the knowledge of the water exchange rate for the BSA-bound GdL complex, the analysis of its NMRD profile at 35 °C
yielded a rotational correlation time of 1.0 ns, one order of magnitude shorter than that of the whole protein. This value
is supported by the longitudinal 17O relaxation rates. This indicates a remarkable internal flexibility, probably due to the relatively large distance between
the protein- and metal-binding moieties of the ligand.
Received: 25 June 1998 / Accepted: 11 August 1998 |
| |
Keywords: | Magnetic resonance imaging Gadolinium(III) complexes Serum albumin Oxygen-17 NMR Nuclear magnetic relaxation dispersion |
本文献已被 SpringerLink 等数据库收录! |
|