Assembly of Bleomycin Saccharide-Decorated Spherical Nucleic Acids.

Glyco-decorated spherical nucleic acids (SNAs) may be attractive delivery vehicles, emphasizing the sugar-specific effect on the outer sphere of the construct and at the same time hiding unfavorable distribution properties of the loaded oligonucleotides. As examples of such nanoparticles, tripodal sugar constituents of bleomycin were synthesized and conjugated with a fluorescence-labeled antisense oligonucleotide (AONARV7). Successive copper(I)-catalyzed azide-alkyne and strain-promoted alkyne-nitrone cycloadditions (SPANC) were utilized for the synthesis. Then, the glyco-AONARV7 conjugates were hybridized with complementary strands of a C60-based molecular spherical nucleic acid (i.e., a hybridization-mediated carrier). The formation and stability of these assembled glyco-decorated SNAs were evaluated by polyacrylamide gel electrophoresis (PAGE), UV melting profile analysis, and time-resolved fluorescence spectroscopy. Association constants were extracted from time-resolved fluorescence data. Preliminary cellular uptake experiments of the glyco-AONARV7 conjugates (120 nM solutions) and of the corresponding glyco-decorated SNAs (10 nM solutions) with human prostate cancer cells (PC3) showed an efficient uptake in each case. A marked variation in intracellular distribution was observed.

Efficient routes toward the synthesis of the D-rhamno-trisaccharide related to the A-band polysaccharide of Pseudomonas aeruginosa.

The present work describes efficient avenues for the synthesis of the trisaccharide repeating unit [α-D-Rhap-(1→3)-α-D-Rhap-(1→3)-α-D-Rhap] associated with the A-band polysaccharide of Pseudomonas aeruginosa. One of the key steps involved 6-O-deoxygenation of either partially or fully acylated 4,6-O-benzylidene-1-thiomannopyranoside by radical-mediated redox rearrangement in high yields and regioselectivity. The D-rhamno-thioglycosides so obtained allowed efficient access to the trisaccharide target via stepwise glycosylation as well as a one-pot glycosylation protocol. In a different approach, a 4,6-O-benzylidene D-manno-trisaccharide derivative was synthesized, which upon global 6-O-deoxygenation followed by deprotection generated the target D-rhamno-trisaccharide. The application of the reported regioselective radical-mediated deoxygenation on 4,6-O-benzylidene D-manno thioglycoside (hitherto unexplored) has potential for ramification in the field of synthesis of oligosaccharides based on 6-deoxy hexoses.

FeCl3 mediated arylidenation of carbohydrates.

Glycosides and thioglycosides based on monosaccharides in reaction with benzaldehyde dimethylacetal or p-methoxybenzaldehyde dimethyl acetal undergo FeCl(3)-catalyzed (20 mol%) regioselective 4,6-O-arylidenation producing the corresponding acetals in high yields. FeCl(3) also mediates acetalation of glycosides and thioglycosides of cellobiose, maltose, and lactose affording the corresponding 4',6'-O-benzylidene acetals, which were isolated after their acetylation in situ with acetic anhydride and pyridine. The combined yields (two steps) of these final products are also high (61-84%). The procedure is applicable to a wide variety of functional groups including -OBn.