Shuqin Han

Synthesis of a new amphiphilic glycodendrimer with antiviral functionality.

A new third generation amphiphilic glycodendrimer was synthesized from a stearylamide lysine dendrimer by condensation of the oligosaccharide moiety. By stepwise condensation and deprotection of di-boc lysine from a core of stearyl amide lysine, a third-generation stearylamide lysine dendrimer was constructed. Acetyl cellobiose and glucose units with the carboxylic acid at the end of alkyl chain attached to the reducing end of the sugar moiety was condensed with surface amino groups of the third generation lysine dendrimer, respectively, to give a new stearylamide acetylcellobiose and acetylglucose lysine dendrimers. The structural analysis was carried out using NMR, IR, and matrix-associated laser desorption/ionization time-of-flight (MALDI TOF) mass spectroscopies. After deacetylation to recover hydroxyl groups and subsequent sulfation, the third-generation sulfated cellobiose stearylamide lysine dendrimer was preliminarily found to have high anti-HIV activity at a 50% effective concentration (EC(50)) as low as 6.4 μg/ml and low cytotoxicity at a 50% cytotoxic concentration (CC(50)) as high as 1000 μg/ml, indicating that the dendrimer gave the enhancement of the functionality of oligosaccharides with low molecular weights. The glycodendrimer with a hydrophobic stearyl chain is immobilized on hydrophobic surfaces by hydrophobic interaction and is expected to provide a new biomedical material with the surface functionality of hydrophilic sulfated oligosaccharides.

Synthesis of oligosaccharide-branched ribofuranan by ring-opening polymerization of a new anhydroribo trisaccharide monomer.

A new anhydroribotrisaccharide monomer, A2B3LR (1), was synthesized and ROP was carried out to elucidate the polymerizability and to obtain oligosaccharide-branched polysaccharides with defined structures. The new trisaccharide monomer was found to be polymerized readily with BF(3) . OEt(2) as a catalyst at -40 degrees C to give a lactose-branched polymer. Copolymerization with ADBR gave the corresponding copolymers in good yields. After removal of protective benzyl groups, D-lactose-branched ribofuranans with free hydroxyl groups were obtained in good yields. The structure of polymers was analyzed by (1)H, 13C, and two-dimensional NMR measurements, suggesting that D-lactose-branched ribofuranans had (1 --> 5)-alpha stereoregularity.

Sugar Functionalized Synergistic Dendrimers for Biocompatible Delivery of Nucleic Acid Therapeutics

Sugars containing cationic polymers are potential carriers for in vitro and in vivo nucleic acid delivery. Monosaccharides such as glucose and galactose have been chemically conjugated to various materials of synergistic poly-lysine dendrimer systems for efficient and biocompatible delivery of short interfering RNA (siRNA). The synergistic dendrimers, which contain lipid conjugated glucose terminalized lysine dendrimers, have significantly lower adverse impact on cells while maintaining efficient cellular entry. Moreover, the synergistic dendrimers complexed to siRNA induced RNA interference (RNAi) in the cells and profoundly knocked down green fluorescence protein (GFP) as well as the endogenously expressing disease related gene Plk1. The new synergic dendrimers may be promising system for biocompatible and efficient siRNA delivery.

Sulfated Alkyl Glucopyranans with Potent Antiviral Activity Synthesized by Ring-Opening Copolymerization of Anhydroglucose and Alkyl Anhydroglucose Monomers

Sulfated glucopyranans having long alkyl groups were prepared by the ring-opening copolymerization of benzylated 1,6-anhydroglucopyranose with 3-O-octadecyl 1,6-anhydro-β- D-glucopyranose monomers, and subsequent deprotection and sulfation. Water-soluble sulfated glucopyranans with 2.8 and 4.7 mol% of 3-O-octadecyl group and lower molecular weights of = 2.5 × 103–5.1 × 103 have potent anti-HIV activity at 0.05–1.25 μg/mL, even though sulfated polysaccharides with molecular weights below = 6 × 103 had low anti-HIV activity. The interaction with poly- L-lysine as a model compound of proteins was analyzed by SPR, DSL, and zeta potential, indicating that the sulfated 3-O-octadecyl glucopyranans had high association and low dissociation rate constants, and the particle size increased after addition of poly- L-lysine. The anti-HIV activity was induced by electrostatic interaction between sulfate groups and amino groups of poly- L-lysine and by the synergistic effect of the hydrophobic long alkyl chain and hydrophilic sulfated group.