Using the carbohydrate cancer marker, TN-antigen (α-GalNAc-OR), covalently linked to a bipyridine core, square planar complexes were formed by self-assembly upon simple addition of Cu(II) sulfate. The required α-d-GalNAc-OR building block was constructed from 2-azidoethyl 2-acetamido-2-deoxy-α-d-glucopyranoside (GlcNAc) by epimerization at C-4 of a suitably protected derivative followed by conventional modifications to provide 2-aminoethyl 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-d-galactopyranoside. The 2-aminoethyl aglycone was further elongated into a key monomer having an aminocaproic acid spacer together with their corresponding dimers using a double N-alkylation strategy of their N-bromoacetyl derivatives using mono-Boc-1,4-diaminobutane, respectively. The building blocks containing the bipyridyl dimers, having either a short or a long spacer arm, together with the tetramer built from the short spacer derivative were prepared in a convergent manner using 2,2′-bipyridine-4,4′-dicarboxylic acid chloride and the aminated sugar derivatives, respectively. Copper(II)-nucleated GalNAc derivatives containing four and eight residues were obtained from an aqueous solution of the bipyridyl derivatives. The relative inhibitory potencies of these glycodendrimers were evaluated against monomeric allyl α-d-GalNAc using a solid-phase competition assay with asialoglycophorin and horseradish peroxidase-labeled lectin Vicia villosa. The di- and tetra-valent bipyridyl clusters showed up to 87-fold increased inhibitory properties (IC50 7.14, 1.82, 4.09 μM, respectively) when compared to the monomer (IC50 158.3 μM) while the Cu(II)-complexes showed up to a 259-fold increase potencies (IC50 0.61 μM) with the octamer showing the highest affinity. However, when expressed on a per-saccharide basis, the tetramer Cu(II) nucleated derivative, possessing the longest inter-sugar distances showed the highest affinity (IC50 0.63 μM). 相似文献
A novel water‐soluble fluorescent glycodendrimer based on perylene bisimides is synthesized, which exhibits high fluorescence quantum yield of 54%. While the binding interactions of PBI‐Man with Concanavalin A (Con A) are studied by fluorescence spectra and CD spectra, which show strong binding affinity for Con A with the binding constant of 3.8 × 107m −1 for monomeric mannose, nearly four orders of magnitude higher affinity than the monovalent mannose ligand. Furthermore, the fluorescence imaging of macrophage cell with PBI‐Man is investigated, and shows selectively binding interaction with the mannose receptor‐medicated cell entry. Moreover, the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) activities of PBI‐Man show that PBI‐Man as a biocompatible agent is noncytotoxic to living cells.