Elucidation of anti-HIV mechanism of sulfated cellobiose–polylysine dendrimers

Three new spherical sulfated cellobiose–polylysine dendrimers of increasing generations bearing negatively charged sulfate groups were prepared by sulfating the corresponding cellobiose–polylysine dendrimers. The first, second, and third-generation derivatives exhibited potent anti-HIV activity with EC50 values of 3.7, 0.6, and 1.5 μg/mL, respectively, in constant to sulfated oligosaccharides with low anti-HIV activity, while the second-generation sulfated dendrimer was the most active. Surface plasmon resonance measurements with poly-l-lysine bearing positively charged amino acids as a model of the HIV surface glycoprotein gp120, indicated that the second-generation dendrimer had the lowest dissociation constant (KD = 1.86 × 10−12 M). Both the particle size and ζ potential increased in the presence of poly-l-lysine. It was proven that the moderate distance between the terminal sulfated cellobiose units in the second-generation dendrimer favored the high anti-HIV activity, owing to the electrostatic interactions developed due to the cluster effect. [Display omitted] •New sulfated cellobiose−polylysine dendrimers were synthesized.•The 2nd generation dendrimer had the highest anti-HIV activity.•The distance between sulfated cellobiose plays an important role on HIV interaction.•The SPR and DLS suggest the electrostatic interaction due to the cluster effect.