Synthesis and Anti-HIV Activity of Sulfated Oligosaccharide-Branched β-CD

Abstract

Sulfated heptakis-6-[4-(β-D-maltopyranosyloxymethyl)-1H-1, 2, 3- triazoyl-1-yl)-β-CD (6-O-maltosyl β-CD) was prepared by the sulfation of 6-O-maltosyl β-CD that had been synthesized by click reaction of acetylated 1-O-propagyl-β-D-maltoside with heptakis-6-azido β-CD and then deacetylation. Sulfated 6-O-glucosyl β-CD was also synthesized from 6-O-glucosyl β-CD. These sulfated β-CDs were found to have potent anti-HIV activity (EC₅₀) of 1.3 and 27.9 µg/mL, respectively, however, sulfated β-CD had low anti-HIV activity,>200 µg/mL. The surface plasmon resonance against poly-L-lysine as a model of HIV surface glycoprotein gp 120 indicated that the apparent association- (k_a) and dissociation-rate (k_d) constants increased and decreased, respectively, k_a=0.21×10³, 6.24×10³, 1.46×10⁴ 1/Ms and k_d=6.70×10^－4, 3.92×10^－4, 3.03×10^－4 1/s, by depending on the number of branched glucose units. The particle size of the sulfated β-CDs was 13.7 nm, 6.2 nm, and 3.3 nm,respectively, measured by dynamic light scattering. These results suggest that the particle size of the sulfated β-CDs also played an important role in the strength of anti-HIV activity. The highest anti-HIV activity of sulfated 6-O-maltosyl β-CD was expressed by the electrostatic interaction with HIV gp 120 putting on sulfated 6-O-maltosyl β-CD like a cap, because the particle size (13.7 nm) was somewhat larger than that of HIV gp 120 (8 to 10 nm).