Multifaceted glycodendrimers with programmable bioactivity through convergent, divergent, and accelerated approaches using polyfunctional cyclotriphosphazenes

Abstract

We report the sequential construction of a set of multivalent structures using cyclotriphosphazene (CTP) units, which were extensively used as primary or secondary cores implementing branching. The utilization of classical convergent and divergent approaches, together with accelerated dendritic strategies comprising orthogonal sequences, double-exponential and double-stage methodologies will be documented and discussed. Straightforward generation of non-conventional glycodendritic systems with surfaces rich in selectable headgroups, despite a low number of dendrimer generation, was achieved with the efficient assembly of highly functionalized AB₃ and AB₅ nanosynthons. The versatility of the methodology allowed access to a wide variety of structurally diversified platforms. The synthesis was completed by peripheral functionalization with spacered saccharides. The resulting architectures can be drawn as classical globular topologies, also dumbbell shapes and “onion peel” design, referred to as hypercores, wedged hypermonomers, glycoclusters, and glycodendrimers. The convenient implementation of controlled topological diversification is considered instrumental for providing sensitive and potent tools to delineate rules for structure–activity relationships in carbohydrate–protein (lectin) interactions, with possibility to tailor size, valency, ligand density, and topology. To illustrate the applicability of this approach for construction of biologically active glycoconjugates, competitive surface plasmon resonance studies were performed with a bacterial virulence factor and a human adhesion/growth-regulatory lectin and showed multivalent effects.