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Sequence-defined glycomacromolecules

Sequence-defined glycomacromolecules

Carbohydrates take part in many biological processes like intercellular recognition and pathogen infections, often involved with multivalent presentation of the saccharide ligands.In nature as well as in artificial systems, single sugar-protein interactions are usually weak and only the simultaneous binding of multiple sugar ligands results a strong and selective interaction.

A straightforward way to mimic such natural multivalent interactions and thereby derive simpler, synthetic mimetics of complex glycans and glycan conjugates is the attachment of sugars to a polymeric scaffold to obtain so-called glycomacromolecules or glycopolymers. It is well known that the number, density and distancing of the sugar ligands along the polymeric scaffold has a strong influence on the resulting binding properties, such as overall avidity and selectivity. Furthermore, there are strong indications that also properties of the polymer backbone e.g., whether it is linear or branched, as well as the linker between backbone and sugar ligand have tremendous influence on the resulting binding. However, most systems so far are optimized empirically and very little is known about the underlying structure-property relations for such glycopolymer ligands. Therefore, our approach is based on the combination of solid phase polymer synthesis and conjugation of sugars to sequence-defined macromolecular scaffolds to obtain highly controlled structures that we can use as model systems for systematic structure-property studies.

We have already shown that our precision glycomacromolecules will help to find improved design rules for novel glycoligands with high affinity and potentially selectivity. Currently, we apply these rules for the synthesis and evaluation of precision glycomacromolecules for various biotechnological and biomedical applications such as pathogen detection, targeted drug delivery, antiviral and antibacterial therapy.

Figure: Using solid phase polymer synthesis to create sequence-defined multivalent glycomacromolecules and examples for variations obtainable in homomultivalent glycomacromolecules.
Figure: Using solid phase polymer synthesis to create sequence-defined multivalent glycomacromolecules and examples for variations obtainable in homomultivalent glycomacromolecules.