Glycan foldamers: designing oligosaccharides to build three-dimensional architectures

Introduction

Natural biopolymers have inspired the development of synthetic analogues, i.e., foldamers, capable of adopting defined conformations and forming programmable three-dimensional architectures. These compounds are mainly based on peptides and nucleic acids, which are well understood at the molecular level.

Potential of Carbohydrates

The diversity, intrinsic chirality, and ability to generate hierarchical assemblies suggest that carbohydrates hold an even larger potential for the generation of three-dimensional structures. However, the complexity of carbohydrate synthesis and structural analysis has prevented access to synthetic carbohydrates capable of adopting defined geometries.

Project Proposal

I propose the creation of carbohydrate foldamers capable of:

1. Adopting rigid secondary structures
2. Assembling into supramolecular architectures

To achieve these goals, we will address fundamental questions related to carbohydrate structure, design new methods to stabilize particular conformations, and implement protocols for systematic structural analysis.

Methodology

State-of-the-art synthetic platforms (i.e., automated glycan assembly) and analytical techniques (i.e., NMR spectroscopy, microED, and single molecule imaging) will be the tools to complete this ambitious project. My group has proved to be very successful at gaining a basic understanding of carbohydrate structure and aggregation.

Future Directions

Building upon these preliminary results, I aim to develop programmable carbohydrate architectures, which have the potential to open a new field of carbohydrate and supramolecular chemistry.

Applications

Analogous to the birth of a new field after the discovery of peptide-based foldamers, carbohydrate foldamers could find applications in several areas, including:

• Material science
• Biology
• Catalysis

Moreover, carbohydrate foldamers will expand our understanding of carbohydrate structures and interactions, and new analytical protocols will standardize the characterization of carbohydrate materials.