Effect of Nonenzymatic Glycosylation on the Magnetic Resonance Imaging (MRI) Contrast Agent Binding to Human Serum Albumin
Department of General, Organic and Biomedical Chemistry, NMR and Molecular Imaging Laboratory, University of Mons, 19 Avenue Maistriau, B-7000 Mons, Belgium. Journal of Medicinal Chemistry
(Impact Factor: 5.45).
03/2012; 55(8):4015-9. DOI: 10.1021/jm3000246
Enhanced nonenzymatic glycosylation (NEG) of human serum albumin (HSA) is observed in diabetic patients. This modifies some of the physiological functions of HSA, as the binding of ligands. Some gadolinium complexes, commonly used as MRI contrast agents, have a high affinity for HSA, which enhances their efficacy. The aim of this study is to evaluate the possible influence of the NEG of HSA on its affinity for some gadolinium chelates.
Available from: Jian Luo
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ABSTRACT: The gadolinium(III) complexes GdL1 and GdL2 were designed as Zn2+-responsive bimodal magnetic resonance imaging (MRI) and fluorescence imaging probes. Upon binding to Zn2+ ions, GdL1 exhibits a bidentate or tridentate mode to form heterodinuclear GdL1Zn or heterotrinuclear (GdL1)2Zn, whereas GdL2 binds to the Zn2+ ion only in a bidentate mode to form (GdL2)2Zn. The gadolinium(III) complexes derived from both H3L1 and H3L2 exhibit remarkable interactions with human serum albumin (HSA) at both site I and site II, which result in significant enhancements of the relaxivity and remarkable improvements of T1-weighted imaging contrast. In the presence of HSA, both the relaxivity (r1) and fluorescence exhibit 300 % enhancement with a clear blueshift of the fluorescence for GdL1Zn, which is ascribed to direct binding to HSA through the formation of a Zn–HSA coordination bond. In contrast, the presence of HSA induces smaller relaxivity increases for GdL1 (155 %), (GdL1)2Zn (183 %), GdL2 (192 %), and (GdL2)2Zn (181 %); these increases are ascribed to weaker hydrophobic interactions or stereospecificity with HSA. The contrast of T1-weighted phantom MR images of these gadolinium(III) complexes in human serum (HS) is much improved relative to that in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) buffer solutions.
Berichte der deutschen chemischen Gesellschaft 07/2014; 2014(20). DOI:10.1002/ejic.201402197 · 2.94 Impact Factor
Available from: Alexey Chubarov
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ABSTRACT: Straightforward and reliable tools for in vivo imaging of tumors can benefit the studies of cancer development, as well as contribute to successful diagnosis and treatment of cancer. (19)F NMR offers an exceptional quantitative way of in vivo imaging of the infused agents because of the lack of (19)F signals from the endogenous molecules in the body. The purpose of this study is to develop molecular probes with appropriate NMR characteristics and the biocompatibility for in vivo applications using (19)F MRI. We have studied the reaction between perfluorotoluene and homocysteine thiolactone resulting in the formation of N-substituted homocysteine thiolactone derivative. It has been shown that the reaction occurs selectively at the para position. This fluorine-labeled homocysteine thiolactone has been employed for the introduction of a perfluorotoluene group as a (19)F-containing tag into human serum albumin. The modified protein has been studied in terms of its ability to aggregate and promote the formation of free radicals. By comparing the properties of N-perfluorotoluene-homocystamide of albumin with N-homocysteinylated albumin, it has been revealed that blocking of the alpha-amino group of the homocysteine residue in the fluorinated albumin conjugate inhibits the dangerous aggregation process, as well as free radical formation. A dual-labeled albumin-based molecular probe for (19)F MRI and fluorescence microscopy has been obtained by functionalizing the protein with both maleimide of a fluorescent dye and a fluorinated thiolactone derivative. The incubation of cells with this conjugate did not reveal any significant reduction in cell viability with respect to the parent albumin. The perfluorotoluene-labeled albumin has been demonstrated to act as a promising agent for in vivo (19)F MRI.
Bioorganic & medicinal chemistry 09/2015; 23(21). DOI:10.1016/j.bmc.2015.09.043 · 2.79 Impact Factor
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