Sequence-Defined Glycopolymer Segments Presenting Mannose: Synthesis and Lectin Binding Affinity

Abstract

We present for the first time the synthesis of sequence-defined monodisperse glycopolymer segments via solid-phase polymer synthesis. Functional building blocks displaying alkyne moieties and hydrophilic ethylenedioxy units were assembled stepwise on solid phase. The resulting polymer segments were conjugated with mannose sugars via 1,3-dipolar cycloaddition. The obtained mono-, di-, and trivalent mannose structures were then subject to Con A lectin binding. Surface plasmon resonance studies showed a nonlinear increase in binding regarding the number and spacing of sugar ligands. The results of Con A lectin binding assays indicate that the chemical composition of the polymeric scaffold strongly contributes to the binding activities as well as the spacing between the ligands and the number of presented mannose units. Our approach now allows for the synthesis of highly defined glycooligomers and glycopolymers with a diversity of properties to investigate systematically multivalent effects of polymeric ligands.

Recent Advances in Solid Phase Polymer Synthesis: Polyamides from Tailor-Made Building Blocks

“…To enable the use of non phosphonium based reagents and further improve coupling efficiency, we recently introduced the so-called dimer building block approach (27,28) The following subchapter will discuss the design and synthesis of suitable dimer building blocks via the coupling of diamine and diacid units in solution prior to solid phase synthesis. This coupling approach can be combined with a broad range of peptide coupling chemistry protocols and thus ensures higher coupling efficiency, reduced byproduct formation and accessibility of longer structures, in combination with a large variety of main and side chain functionalities (27)(28)(29)(30)(31)(32)(33)(34).…”

“…This coupling approach can be combined with a broad range of peptide coupling chemistry protocols and thus ensures higher coupling efficiency, reduced byproduct formation and accessibility of longer structures, in combination with a large variety of main and side chain functionalities (27)(28)(29)(30)(31)(32)(33)(34).…”

“…The secondary amine can then be used for the attachment of various side chains or protecting groups via amide coupling e.g. with pentynoic acid or pentenoyl acid chloride (27,32). In the final step, the trityl group is cleaved releasing again a free primary amine that is used for the condensation with succinic anhydride leading to the final building block.…”

Simultaneous Control over Monomer Sequence and Molecular Weight Using the RAFT Process

“…Whereas step-growth polymerizations can be adopted towards sequence control with relative ease (e.g. using solid-phase synthesis (8)(9)(10)(11) or the ligation of oligomers (12,13)), the development of methods suitable for chain-growth polymerization are scarce, and real sequence control is currently limited to the synthesis of alternating or AAB-periodic copolymers (vide infra).…”

Peptide-Polymer Conjugates as Model Systems To Explore the Functional Space of Precision Polymers

“…via solid-phase synthesis (10)(11)(12). Solid-phase synthesis methods have been widely applied to the synthesis of biopolymers (nucleic acids, peptides and sugars) but can also be applied to other monomers (13)(14)(15)(16)(17)(18). Though limitations still exist, polymers prepared through a step-growth polymerization can therefore be used for the creation of functional materials (for applications in coatings, drug-delivery, catalysis, etc.)…”