Design and sustainable synthesis of small mannose-based glycodendrons as ligands for HIV-1 envelope protein gp120: Toward an explanation for their binding

Abstract

On the basis of the interesting properties that glucuronic acid-based glycodendrimers and glycodendrons show against Dengue virus through their interaction with its envelope protein, herein we describe the design, sustainable synthesis and anti HIV-1 evaluation of a series of mannose-based glycodendrimers bearing different scaffolds, valency and functional groups at the focal position. Their sustainable chemical synthesis was performed using microwave-assisted copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) reaction to yield glycoconjugates with full conversions (99%), allowing the reduction of the reaction time from 16 h to 60–120 min. Surface plasmon resonance studies have demonstrated that the small mannose-based glycodendrons (divalent derivatives) give the best binding interactions with the HIV-1 gp120 envelope protein, being the most active those that have a methoxymethyl group or an azidomethyl group at the focal position. Molecular modeling studies were carried out to simulate and explain the binding observed by surface plasmon resonance. This work reports a sustainable synthesis of small mannose-based glycodendrons as novel and potent anti HIV lead compounds.