Synthesis of a glycan hairpin

The research was first published online [July 3^rd, 2023] in the journal Nature Chemistry.

Carbohydrates constitute approximately 80% of the biomass of our planet - half on land and the other half in the sea. However, its material properties are still poorly understood. Knowledge about natural proteins has been used to design synthetic peptide sequences that could take on programmable 3D shapes and perform specific functions, such as the production of drugs and nanotechnology materials.

A collaborative work led by the Max Planck Institute of Colloids and Interfaces (MPICI), succeeded in designing, for the first time, a carbohydrate sequence capable of folding into a stable secondary structure. Until now, sugars were considered too flexible to assume a stable conformation and such self-folding biopolymers had only been developed for proteins and DNA. In this work, Dr. Delbianco and collaborators, including Jesús Jiménez Barbero, scientific director of CIC bioGUNE, showed that it is possible to design glycans that adopt a specific stable conformation. The authors linked natural sugar motifs to generate a shape that does not exist in nature, resembling a hairpin. In a similar approach to that used in Lego, two linear rods containing fragments of cellulose were connected to a rigid glycan twist to obtain a new unnatural shape.

"Carbohydrates can be generated with programmable forms, which opens up the possibility of giving glycans new properties and functions", says Dr. Martina Delbianco. The scaffold was rapidly prepared using the methodology known as "Automated Glycan Assembly" (AGA), a process in which monosaccharides are connected using an automated synthesizer to generate custom polysaccharide sequences.

To reveal the three-dimensional structure of the designed molecule, a large number of methodologies were used, especially Nuclear Magnetic Resonance (NMR). These experiments have essentially been carried out in the Chemical Glycobiology group at CIC bioGUNE. "The 3D structure of a biomolecule determines its function. This could mean, for example, that in the future we could use folded sugars as medicines, as catalysts for specific chemical transformations, or as building blocks for the creation of nanomaterials", says Dr. Martina Delbianco.

The scientific advances generated by this research may provide further opportunities, due to its greater abundance and diversity compared to peptides. “Through this multidisciplinary research we have opened new horizons to design and prepare new sustainable molecules based on carbohydrates and discover their three-dimensional structure. Now we must learn to modulate its properties and apply them in nanotechnology and biomedicine”, adds Dr. Jesús Jiménez-Barbero.

About Max Planck Institute of Colloids and Interfaces (MPICI)

The Max Planck Institute of Colloids and Interfaces (MPICI), located in Potsdam (Germany) is a research organisation specialized in chemistry and biology of carbohydrates as well as nano- and microstructures, with a particular focus on learning from nature how to build hierarchical materials or active systems with new functionalities, with adaptive, self-healing or self-assembling properties.

About CIC bioGUNE

The Centre for Cooperative Research in Biosciences (CIC bioGUNE), member of the Basque Research & Technology Alliance (BRTA), located in the Bizkaia Technology Park, is a biomedical research organisation conducting cutting-edge research at the interface between structural, molecular and cell biology, with a particular focus on generating knowledge on the molecular bases of disease, for use in the development of new diagnostic methods and advanced therapies.

About Ikerbasque

Ikerbasque - Basque Foundation for Science - is the result of an initiative of the Department of Education of the Basque Government that aims to reinforce the commitment to scientific research by attracting, recovering and consolidating excellent researchers from all over the world. Currently, it is a consolidated organization that has 290 researchers/s, who develop their work in all fields of knowledge.