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001-es BibID:BIBFORM115274
035-os BibID:(WoS)001082626400001 (Scopus)85175586211
Első szerző:Malikidogo, Kyangwi P.
Cím:Gd3+ Complexes for MRI Detection of Zn2+ in the Presence of Human Serum Albumin: Structure-Activity Relationships / Kyangwi P. Malikidogo, Manon Isaac, Adrien Uguen, Jean-Fran₀cois Morfin, Gyula Tircsó, Éva Tóth, Célia S. Bonnet
Dátum:2023
ISSN:0020-1669 1520-510X
Megjegyzések:Zn2+-responsive magnetic resonance imaging (MRI) contrast agents are typically composed of a Gd chelate conjugated to a Zn2+-binding moiety via a linker. They allow for Zn2+ detection in the presence of human serum albumin (HSA). In order to decipher the key parameters that drive their Zn2+-dependent MRI response, we designed a pyridine-based ligand, PyAmC2mDPA, and compared the properties of GdPyAmC2mDPA to those of analogue complexes with varying Gd core, Zn-binding moiety, or linker sizes. The stability constants determined by pH potentiometry showed the good selectivity of PyAmC2mDPA for Gd3+ (log KGd = 16.27) versus Zn2+ (log KZn = 13.58), proving that our modified Zn2+-binding DPA moiety prevents the formation of previously observed dimeric species. Paramagnetic relaxation enhancement measurements indicated at least three sites that are available for GdPyAmC2mDPA binding on HSA, as well as a 2-fold affinity increase when Zn2+ is present (KD = 170 ?M versus KDZn = 60 ?M). Fluorescence competition experiments provided evidence of the higher affinity for site II vs site I, as well as the importance of both the Zn-binding part and the Gd core in generating enhanced HSA affinity in the presence of Zn2+. Finally, an analysis of nuclear magnetic relaxation dispersion (NMRD) data suggested a significantly increased rigidity for the Zn2+-bound system, which is responsible for the Zn2+-dependent relaxivity response.
Tárgyszavak:Természettudományok Kémiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Molecular imaging
Zinc
Gadolinium
MRI
Human Serum Albumin
Megjelenés:Inorganic Chemistry. - 62 : 42 (2023), p. 17207-17218. -
További szerzők:Uguen, Adrien Morfin, Jean-François Tircsó Gyula (1977-) (vegyész, kémia tanár) Tóth Éva (1967-) (koordinációs kémia) Bonnet, Célia S.
Pályázati támogatás:K-134694
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