title: The interaction of La(3+) complexes of DOTA/DTPA glycoconjugates with the RCA(120) lectin: a saturation transfer difference NMR spectroscopic study.
abstract: The study of ligand-receptor interactions using high-resolution NMR techniques, namely the saturation transfer difference (STD), is presented for the recognition process between La(III) complexes of 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane monoamide and diethylenetriaminepentaacetic acid bisamide glycoconjugates and the galactose-specific lectin Ricinus communis agglutinin (RCA(120)). This new class of Gd(III)-based potential targeted MRI contrast agents (CAs), bearing one or two terminal sugar (galactosyl or lactosyl) moieties, has been designed for in vivo binding to the asialoglycoprotein receptor, which is specifically expressed at the surface of liver hepatocytes, with the aim of leading to a new possible diagnosis of liver diseases. The in vitro affinity constants for the affinity of the divalent La(III)-glycoconjugate complexes for RCA(120), used as a simple, water-soluble receptor model, were higher than those of the monovalent analogues. The combination of the experimental data obtained from the STD NMR experiments with molecular modelling protocols (Autodock 4.1) allowed us to predict the mode of binding of monovalent and divalent forms of these CAs to the galactose 1α binding sites of RCA(120). The atomic details of the molecular interactions allowed us to corroborate and supported the interaction of both sugar moieties and the linkers with the surface of the protein and, thus, their contribution to the observed interaction stabilities.
authors.affiliation: Department of Life Sciences, Center of Neurosciences and Cell Biology, University of Coimbra, Portugal.
authors.forename: João M C
authors.initials: JM
authors.lastname: Teixeira
authors.forename: David M
authors.initials: DM
authors.lastname: Dias
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Cañada
authors.forename: José A
authors.initials: JA
authors.lastname: Martins
authors.forename: João P
authors.initials: JP
authors.lastname: André
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
authors.forename: Carlos F G C
authors.initials: CF
authors.lastname: Geraldes
mesh_terms: D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism; D006001:Glycoconjugates / Q000737:chemistry / Q000378:metabolism*; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry* / Q000378:metabolism; D007811:Lanthanum / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D004369:Pentetic Acid / Q000737:chemistry* / Q000378:metabolism; D037121:Plant Lectins / Q000302:isolation & purification / Q000378:metabolism*; D011485:Protein Binding; D012278:Ricinus / Q000737:chemistry* / Q000378:metabolism
chemical_list: D003287:Contrast Media; D006001:Glycoconjugates; D006573:Heterocyclic Compounds, 1-Ring; D037121:Plant Lectins; C017707:Ricinus communis agglutinin-1; C071349:1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid; D007811:Lanthanum; D004369:Pentetic Acid