Investigation of non-covalent interactions between paramagnetic complexes and human serum albumin by electrospray mass spectrometry.
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.
NMR Laboratory, Department of Organic Chemistry, University of Mons-Hainaut, 24 Avenue du Champ de Mars, B-7000 Mons, Belgium.
Virginie
V
Henrotte
Sophie
S
Laurent
Valérie
V
Gabelica
Luce Vander
LV
Elst
Edwin
E
Depauw
Robert N
RN
Muller
D001665:Binding Sites; D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism; D005682:Gadolinium / Q000737:chemistry / Q000378:metabolism; D019786:Gadolinium DTPA / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D003287:Contrast Media; C112668:MP 2269; D012709:Serum Albumin; D005682:Gadolinium; D019786:Gadolinium DTPA