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Imaging of biomolecules guides our understanding of their diverse structures and functions1,2. Real-space imaging at sub-nanometre resolution using cryo-electron microscopy has provided key insights into proteins and their assemblies3,4. Direct molecular imaging of glycans-the predominant biopolymers on Earth, with a plethora of structural and biological functions5-has not been possible so far6. The inherent glycan complexity and backbone flexibility require single-molecule approaches for real-space imaging. At present, glycan characterization often relies on a combination of mass spectrometry and nuclear magnetic resonance imaging to provide insights into size, sequence, branching and connectivity, and therefore requires structure reconstruction from indirect information7-9. Here we show direct imaging of single glycan molecules that are isolated by mass-selective, soft-landing electrospray ion beam deposition and imaged by low-temperature scanning tunnelling microscopy10. The sub-nanometre resolution of the technique enables the visualization of glycan connectivity and discrimination between regioisomers. Direct glycan imaging is an important step towards a better understanding of the structure of carbohydrates.


X Wu, M Delbianco, K Anggara, T Michnowicz, A Pardo-Vargas, P Bharate, S Sen, M Pristl, S Rauschenbach, U Schlickum, S Abb, P H Seeberger, K Kern. Imaging single glycans. Nature. 2020 Jun;582(7812):375-378

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PMID: 32555487

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