mass spectrometry; electrospray; noncovalent interactions; human serum albumin; contrast agents; MRI
Abstract :
[en] Stable gadolinium(III) chelates are nowadays routinely used as contrast agents for magnetic resonance imaging (MRI). Their non-covalent binding to human serum albumin (HSA) has shown to improve their efficacy. Non-covalent interactions lead to complex formation that can be quantified by several techniques that are mostly tedious and time-consuming. In this study, electrospray ionization mass spectrometry (ESI-MS) was used to investigate the interaction between HSA and several gadolinium(III) complexes. The results were compared with those obtained in the liquid phase. Four gadolinium complexes were investigated: Gd-DTPA 1, Gd-C4Me-DTPA 2, Gd-EOB-DTPA 3, and MP-2269 4. Relaxometry studies show that complexes 1 and 2 have no significant affinity for HSA, while complexes 3 and 4 have increasing affinities for the protein. 1:1 and 1:2 complexes between HSA and MP-2269 were detected by ESI-MS for a twofold excess of the contrast agent, whereas a ligand/protein molar ratio of 4:1 was necessary to observe a 1:1 stoichiometry for Gd-EOB-DTPA, an observation that is in good agreement with the known weaker affinity of the contrast agent for the protein. At a fourfold molar excess, no supramolecular complex was observed for Gd-DTPA I and Gd-C4Me-DTPA 2; a tenfold molar excess was necessary to detect a 1:1 complex, confirming the very weak affinity of these contrast agents for HSA.
Research Center/Unit :
CART - Centre Interfacultaire d'Analyse des Résidus en Traces - ULiège
Disciplines :
Chemistry
Author, co-author :
Henrotte, Virginie; Université de Mons-Hainaut > Département de Chimie Organique > Laboratoire de RMN
Laurent, Sophie ; Université de Mons-Hainaut > Département de Chimie Organique > Laboratoire de RMN
Gabelica, Valérie ; Université de Liège - ULiège > Département de Chimie (Sciences) > Chimie physique, spectrométrie de masse
Vander Elst, Luce; Université de Mons-Hainaut > Département de Chimie Organique > Laboratoire de RMN
De Pauw, Edwin ; Université de Liège - ULiège > Département de Chimie (Sciences) > Chimie physique, spectrométrie de masse
Muller, Robert N; Université de Mons-Hainaut > Département de Chimie Organique > Laboratoire de RMN
Language :
English
Title :
Investigation of non-covalent interactions between paramagnetic complexes and human serum albumin by electrospray mass spectrometry
Publication date :
2004
Journal title :
Rapid Communications in Mass Spectrometry
ISSN :
0951-4198
eISSN :
1097-0231
Publisher :
John Wiley & Sons, Inc, Chichester, United Kingdom