Previously, we have established the solid phase polymer synthesis of so-called precision glycomacromolecules. Based on the step-wise assembly of tailor-made building blocks on solid support, monodisperse and sequence-controlled oligo(amidoamine) scaffolds were synthesized that allow for the multivalent presentation of sugar ligands. Here we extend on this concept using a split & combine approach to have access to a small library of linear and branched glycomacromolecules. First, a novel building block is introduced placing an azide side chain in the scaffold and allowing for Cupper mediated azide-alkyne cycloaddition (CuAAC) of readily available propargyl functionalized glycans. After assembly of the linear scaffold on solid support, the resin beads are divided in two, where one part is end capped and further used as scaffold and the other part is functionalized with propargylated α D mannopyranoside in the sidechain, end capped with an alkyne and finally cleaved from solid support. The linear, glycosylated and alkynylated macromolecules are then clicked to the end capped scaffolds via CuAAC to give final branched glycomacromolecules. In this way, precision glycomacromolecules with molecular weights from 2.8 to 6.6 kDa with two and three branches, respectively, have been synthesized carrying two to six sugar residues per molecule. The obtained linear and branched precision glycomacromolecules were then subjected to first binding studies using model lectin Concanavalin A in a direct binding assay via surface plasmon resonance.

Solid phase assisted split & combine approach towards branched precision glycomacromolecules

254th National Meeting (2017)

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