Imaging Single Glycoconjugates

ongoing

GlycoX aims to develop single molecule analytical methods to address the challenge of elucidating glycoconjugate structures. Glycoconjugates are glycans (a.k.a carbohydrates) that are attached to another biomolecules such as proteins or lipids. Glycoconjugates are essential to all living organisms, carrying out key cell-cell communication roles in immune system or in microbial infection. Glycoconjugates are found in all biological systems and yet, when compared to proteins or nucleotides, very little is known about their structures and how they lead to their biochemical properties or how they can be exploited in therapeutics. Efforts to reveal their structures by ensemble averaged approaches, whether primary structures (sequences) or secondary structures (conformations), have been severely hampered by the high complexity and flexibility of glycans. GlycoX addresses this challenge by direct imaging of single glycoconjugate molecules, devoid of any ensemble averaging. To this end, glycoconjugate ions generated from electrospray ionization are soft landed on surface and imaged one-at-a-time by scanning probe microscopy in vacuo. The Project proposes the use of direct imaging (1) to identify the glycoforms of any glycoconjugates (i.e. variants of a specific glyconjugate that possess different glycan primary structures), (2) to sequence any glycan residues in any glycoconjugates, and (3) to determine the conformations of any glycoconjugates. The Project plans to focus on glycoconjugates that are intractable by present analytical methods, many of which are central in immune system, in microbial infection, and in emerging diagnostics, drugs, and vaccines. These works have far reaching impacts: shedding light into the language used by cells to communicate and by pathogens to infect; creating new opportunities in glycan-based therapeutics; as well as opening new frontiers in single molecule analytical chemistry of biomolecules.