Synthesis and structural characterization of longer-chain glycan

Glycans that make up the cell wall of bacteria play a key role in the dynamic interaction with the host, activating and modulating its immune response. The molecular details of this interaction are not yet fully understood precluding their broad use in pharmaceutical and biomedical fields. In fact, the development of robust strategies for the synthesis and characterization of well-defined glycan structures is nowadays a top priority and has an enormous impact in various biomedical fields. In this context, various synthetic carbohydrate-based vaccines or even glycoconjugate-based vaccine adjuvants have been produced. A limitation in this field, however, is the difficulty in synthesizing and characterizing long-chain glycans.

An important step forward in this field comes from a study carried out by Professor Alba Silipo of the Department of Chemical Sciences at federico II in collaboration with Professor Biao Yu of the Shanghai Institute of Organic Chemistry.

That study, published in the prestigious journal Nature Communications (doi. 10.1038/s41467-020-17992-x), reports the first synthesis of a glycan, of bacterial origin, of length 128-mer and its complete characterization via Nuclear Magnetic Resonance (NMR) Spectroscopy and Mass Spectrometry. The synthesized glycan predicted a [→4)-α-L-ramnopyranose-(1 → 3)-β-D-mannopyranose-(1 → ]_n repeating unit inspired by the polysaccharide portion of the lipopolysaccharide of the bacterium Bacteroidesvulgatus, a key component of the human intestinal microbiota capable of silencing potent inflammatory processes in the intestine.

Professor Silipo 's study establishes a number of firsts. She not only describes the synthesis of the longest linear glycan ever chemically synthesized, but also the longest ever characterized via mass spectrometry (MALDI-FT-ICR-MS) and the longest (in the case of 64-mer) characterized via diffusion NMR spectroscopy (DOSY). Silipo also performed conformational analysis studies and showed that glycan has a degree of flexibility that may explain its biological activity.

This study opens up a number of possibilities as well as inspiring future research on the synthesis and functional studies of pure and homogeneous polysaccharides for various therapeutic purposes.

This research activity is part of the carbohydrate chemistry studies being carried out by the SSCN group, http://www.scienzechimiche.unina.it/ricerca/sccn, of the Department of Chemical Sciences, and adds to Professor Silipo 's further recent success in winning the €3.7 million Marie Skłodowska-Curie Innovative Training Networks "GLYTUNES" project as Coordinator.