Gd(3+) complexes conjugated to Pittsburgh compound B: potential MRI markers of β-amyloid plaques. - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue European Journal of Biochemistry Année : 2014

Gd(3+) complexes conjugated to Pittsburgh compound B: potential MRI markers of β-amyloid plaques.

Résumé

In an effort towards the visualization of β-amyloid (Aβ) plaques by T1-weighted magnetic resonance imaging for detection of Alzheimer's disease, we report the synthesis and characterization of stable, noncharged Gd(3+) complexes of three different 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid monoamide derivatives conjugated to Pittsburgh compound B, a well-established marker of Aβ plaques. The ligands L1, L2, and L3 differ in the nature and size of the spacer linking the macrocyclic chelator and the Pittsburgh compound B targeting moiety, which affects their lipophilicity, the octanol-water partition coefficients of the complexes ranging from -0.15 to 0.32. Given their amphiphilic behavior, the complexes form micelles in aqueous solution (critical micellar concentration 1.00-1.49 mM). The parameters determining the relaxivity, including the water exchange rate and the rotational correlation times, were assessed for the monomeric and the micellar form by a combined (17)O NMR and (1)H nuclear magnetic relaxation dispersion (NMRD) study. They are largely influenced by the aggregation state and the hydrophobic character of the linkers. The analysis of the rotational dynamics for the aggregated state in terms of local and global motions using the Lipari-Szabo approach indicates highly flexible, large aggregates. On binding of the complexes to human serum albumin or to the amyloid peptide Aβ1-40 in solution, they undergo a fourfold and a twofold relaxivity increase, respectively (40 MHz). Proton relaxation enhancement studies confirmed moderate interaction of Gd(L1) and Gd(L3) with human serum albumin, with KA values ranging between 250 and 910 M(-1).
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Dates et versions

hal-01179355 , version 1 (22-07-2015)

Identifiants

  • HAL Id : hal-01179355 , version 1
  • PUBMED : 24297602

Citer

André F Martins, Jean-François Morfin, Carlos F G C Geraldes, Éva Tóth. Gd(3+) complexes conjugated to Pittsburgh compound B: potential MRI markers of β-amyloid plaques.. European Journal of Biochemistry, 2014, 19 (2), pp.281-295. ⟨hal-01179355⟩
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