Premium
Investigation of non‐covalent interactions between paramagnetic complexes and human serum albumin by electrospray mass spectrometry
Author(s) -
Henrotte Virginie,
Laurent Sophie,
Gabelica Valérie,
Elst Luce Vander,
Depauw Edwin,
Muller Robert N.
Publication year - 2004
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.1571
Subject(s) - chemistry , gadolinium , human serum albumin , electrospray ionization , covalent bond , stoichiometry , mri contrast agent , mass spectrometry , electrospray , ligand (biochemistry) , molar mass , relaxometry , supramolecular chemistry , crystallography , chromatography , crystal structure , magnetic resonance imaging , organic chemistry , medicine , biochemistry , receptor , spin echo , radiology , polymer
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‐C 4 Me‐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 1 and Gd‐C 4 Me‐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. Copyright © 2004 John Wiley & Sons, Ltd.