Synthetic biomimetic polymers used to study biological processes should show similar complexity as their natural analogs, <i>e.g.</i> in terms of monomer sequence and dispersity, to allow for new insights into structure-property correlation. There are various methods to obtain sequence-controlled biomimetic polymers, from controlled polymerizations to the use of specific monomers or iterative coupling procedures.<br/>In this work, we present the synthesis and first evaluation of multiblock sequence-controlled polymeric glycomimetics. The glycomimetic polymers are assembled from two alternating blocks, one bearing a defined sequence of Mannose ligands whereas the second block introduces a hydrophilic, non-binding spacer. The multiblock structure is achieved by a combination of iterative coupling of functional building blocks on solid phase resulting in monodisperse, telechelic macromonomers and their later polymerization in a step-growth fashion using thiol-ene click chemistry (TEC). After optimization of the polymerization conditions, a first series of glycopolymers was synthesized with Xn of 8, corresponding to Mn values between 13.4 and 17.5 kDa, depending on the used glycomacromonomer. Subsequently, the resulting glycopolymers were evaluated for their potential as multivalent glycomimetics by studying their binding and clustering of lectin receptor Concanavalin A via turbidity assays, surface plasmon resonance, and single-molecule force spectroscopy measurements. A correlation between the number of Mannose ligands and resulting binding was observed, whereas, surprisingly, the length of the overall glycopolymer seems to have no effect. In order to further increase molecular weights, in a second series of glycopolymers, larger molecular weight PEG was used as macromonomer during TEC polymerization. Further, the alkene moiety of the glycomacromonomers was exchanged by a more reactive norbornene functionality which resulted in significantly higher Xn.

Sequence-controlled polymeric glycomimetics for the investigation of epitope spacing on multivalent ligand/receptor interactions

254th National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.