Synthesis of Neu5Ac-Gal-functionalized gold glyconanoparticles

Abstract

a b s t r a c tNeu5Ac-Gal-containing neoglycoside 1 was convergently synthesized through Cu(I)-catalyzed 1,3-dipolar cycloaddition of methyl (6-azidohexyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-O-a-D-glycero-D-galacto-2-nonulopyranosyl)uronate and 11-thioacetylundecyl 2,4,6-tri-O-benzoyl-3-O-propargyl-b-D-galactopyranoside. The stable and water-soluble gold glyconanoparticle 2 (d = 3.4 nm) has been successfully prepared from neoglycoside 1 and characterized by NMR, IR, and TEM techniques.Ó 2009 Elsevier Ltd. All rights reserved.The well-known cluster glycoside effect 1 has spawned the construction of myriad multivalent glycopolymers for the study of carbohydrate-protein interactions. Integrated nanoparticle-biomolecule multifunctional systems constitute useful tools to mimic the behavior of biomolecules in cells, thus helping to explore the mechanisms of biological process with a variety of potential applications. 2,3 Gold nanoclusters functionalized with carbohydrates provide a well-defined chemical composition to intervene in the cell-cell adhesion and recognition processes where carbohydrates are involved. [4][5][6][7][8] However, assembly of glyconanoparticles from authentic oligosaccharides are rather difficult due to the insufficient quantities and methodology limitations, while the syntheses of these oligosaccharides are complex and often feature low overall yields. 9 The mission may be considerably simplified if target structures are represented by pseudo-oligosaccharides or oligosaccharide mimics in which certain glycosidic bonds are substituted with non-glycosidic motifs. 10-14 Among these efforts, 1,2,3-triazole links have emerged as a popular bridging unit in carbohydrate chemistry because of their facile and efficient method of synthesis, which is referred to as 'click chemistry '. 15,16 This method is based on Cu(I)-catalyzed Huisgen's 1,3-dipolar cycloaddition 17 of azides and terminal alkynes, and it has been successfully applied for the synthesis of various glycoconjugates including multivalent glycosides, 18,19 cyclodextrin analogues, 20 glycopeptide mimetics, 21 and glycosidase inhibitors. 22 Moreover, the triazole core is more than a passive linker because it can participate in hydrogen-bonding and dipole interactions, which can favor the binding to biomolecular targets and improve solubility. 23 In a collaborative project, we were asked to provide neoglycoside 1 and its corresponding gold glyconanoparticle 2 (Fig. 1) as the references for bioactivity studies. We here report the synthesis of this Neu5Ac-Gal-coated gold nanoparticle.The synthesis was first envisaged from the p-methoxyphenyl glycoside 3 24 (Scheme 1). Deacetylation of 3 with NaOMe in MeOH (?4), followed by regioselective propargylation of 3-OH via a dibutyltin intermediate, gave the corresponding 3-O-propargyl galactopyranoside 5 in 80% yield. Benzoylation of 5 with BzCl in pyridine and subsequent conversion of anomeric p-methoxyphenyl (MP) group to trichloroacetimidate were carried out smoothly in the presence of ce...

Systematic Tuning of Fluoro-galectin-3 Interactions Provides Thiodigalactoside Derivatives with Single-Digit nM Affinity and High Selectivity

“…The key step to making the asymmetrical thiodigalactosides 35 – 37 (Scheme ) was the S -glycosylation of the thiogalactoside donor 33 and the galactoside acceptor 34 , facilitated by tetrabutylammonium fluoride, to give thiodigalactoside 35 . Thiogalactoside donor 33 was prepared, starting from the known propargyl derivative 30 , following a published procedure for making 3- O -coumarylmethylgalactosides. Asymmetrical thiodigalactosides 36 – 38 were then obtained from thiodigalactoside 35 through a 1,3-dipolar cycloaddition and subsequent deacetylation by either sodium methoxide or butylamine in methanol.…”

Magnetic nanoparticles with diblock glycopolymer shells give lectin concentration-dependent MRI signals and selective cell uptake

“…Davis et al functionalised gold nanoparticles with tetra-saccharides to detect endothelial markers E-/P-selectin (CD62E/CD62P) in acute brain inammation 20 as well as with a-N-acetyl-D-galactosamine polymers for the synthesis of Tn-antigen glycan anticancer vaccine. 21 Other examples of carbohydrate/glycopolymer functionalized gold nanoparticles [22][23][24][25][26] and quantum dots 27 have been reported for biomedical applications, including tumor-associated glycopeptide antigens and in vivo liver targeting. Natural polysaccharide (including dextran, chitosan, agarose) has been previously used as a polymer coating to stabilize superparamagnetic iron oxide nanoparticles (IONPs) in biological uids.…”

Multifunctional Dendritic Sialopolymersomes as Potential Antiviral Agents: Their Lectin Binding and Drug Release Properties

“…In this context, polymers, 17,18,21−24 dendrimers, 25−30 liposomes, 31−33 gold nanoparticles, 34,35 nanogels, 36 and polymer nanoparticles 37 functionalized with Neu5Ac have been proposed as potential inhibitors of influenza virus infection. Because of their high multivalency, multifunctional capabilities, tunable size, and morphological resemblance to mammalian cells, polymersomes are attractive scaffolds for the study of carbohydrate−protein interactions 38−44 and for the potential development of therapeutics and vaccines.…”

“…To achieve inhibition at lower concentrations, Neu5Ac has been conjugated to various scaffolds to obtain multivalent displays. In this context, polymers, ,,− dendrimers, − liposomes, − gold nanoparticles, , nanogels, and polymer nanoparticles functionalized with Neu5Ac have been proposed as potential inhibitors of influenza virus infection.…”