Glycan Mimetics for Cell Glycocalyx Reconstitution: a polymer chemist’s approach to fight infection

Objective

The aim of GLYMCE is to understand how carbohydrates and their assemblies are recognized by pathogens to drive infections. The identified molecular patterns will be transferred to biomimetic glycopolymer materials to extend the arsenal for the fight against infections.

Importance of Carbohydrates

Carbohydrates are not just sweet; they are crucial in various biological interactions. Cell surfaces are covered in carbohydrates, the glycocalyx, that governs contact with pathogens such as viruses and bacteria.

Role of Glycosaminoglycans

A class of carbohydrates critical for pathogen attachment and infections are glycosaminoglycans (GAGs). GAGs are highly diverse polysaccharides already used in medicine (e.g., heparin against thrombosis).

1. The potential of GAGs in fighting viral and bacterial infections has been recognized in biology and medicine.
2. However, as of today, there are no GAG-based drugs used for this purpose.
3. A key limitation is insufficient knowledge about the mode of action of GAGs within the complex ensemble of the glycocalyx.

Research Questions

How does the display of GAGs within the glycocalyx affect their pathogen interactions?

Methodology

GLYMCE will tackle this question from the polymer chemist’s point of view by taking a bottom-up approach:

1. Prepare GAG mimetics (level 1).
2. Assemble glycocalyx mimetics and study their spatial organization of GAGs upon pathogen binding (level 2).
3. Reengineer the glycocalyx of living cells to understand the factors governing infection (level 3).

This is only now possible through recent synthetic tools developed by my lab, enabling GAG mimetics with controlled sequence, molecular weight, chain conformation, architecture, and sulfation patterns – all parameters known to critically impact the affinity and selectivity of GAGs.

Overall Impact

Overall, by taking a radically different approach informed by chemical biology and brought to life by polymer chemistry, mechanisms for GAG-mediated pathogen attachment will be derived and applied to develop new materials and strategies to detect, prevent, and treat infections.