A Sulfur Tripod Glycoconjugate that Releases a High-Affinity Copper Chelator in Hepatocytes

Anais M Pujol (1) , Martine Cuillel (2) , Anne-Solène Jullien (1) , Colette Lebrun (1) , Doris Cassio (3) , Elisabeth Mintz (2) , Christelle Gateau (1) , Pascale Delangle (1)

1 SCIB - UMR E3 - Service de Chimie Inorganique et Biologique
2 LCBM - UMR 5249 - Laboratoire de Chimie et Biologie des Métaux
3 INSERM UMRS757

Released in the cell: Three N-acetylgalactosamine units, which recognize the asialoglycoprotein receptor, were tethered through disulfide bonds to the three coordinating thiol functions of a sulfur tripod ligand that has a high affinity for CuI (see scheme). The resulting glycoconjugate can be considered as a prodrug, because after uptake by hepatic cells the intracellular reducing glutathione (GSH) releases the high-affinity intracellular CuI chelator.

Mots clés: bioinorganic chemistry; cell recognition; copper; drug delivery; glycoconjugates; ASIALOGLYCOPROTEIN RECEPTOR; N-ACETYLGALACTOSAMINE; GENE DELIVERY; DISEASE; BINDING; CU(I); IDENTIFICATION; SELECTIVITY; ANTIBODIES; LIGANDS

Domaines: Chimie inorganique; Biologie cellulaire; Sciences pharmaceutiques

Anais M Pujol, Martine Cuillel, Anne-Solène Jullien, Colette Lebrun, Doris Cassio, et al.. A Sulfur Tripod Glycoconjugate that Releases a High-Affinity Copper Chelator in Hepatocytes. Angewandte Chemie International Edition, 2012, 51 (30), pp.7445-7448. ⟨10.1002/anie.201203255⟩. ⟨hal-01131306⟩