Cryogenic Infrared Spectroscopy Reveals Structural Modularity in the Vibrational Fingerprints of Heparan Sulfate Diastereomers

Lettow, Maike; Grabarics, Márkó; Greis, Kim; Mucha, Eike; Thomas, Daniel A.; Chopra, Pradeep; Boons, Geert-Jan; Karlsson, Richard; Turnbull, Jeremy E.; Meijer, Gerard; Miller, Rebecca L.; von Helden, Gert; Pagel, Kevin

Abstract

Heparan sulfate and heparin are highly acidic polysaccharides with a linear sequence, consisting of alternating glucosamine and hexuronic acid building blocks. The identity of hexuronic acid units shows a variability along their sequence, as d-glucuronic acid and its C5 epimer, l-iduronic acid, can both occur. The resulting backbone diversity represents a major challenge for an unambiguous structural assignment by mass spectrometry-based techniques. Here, we employ cryogenic infrared spectroscopy on mass-selected ions to overcome this challenge and distinguish isomeric heparan sulfate tetrasaccharides that differ only in the configuration of their hexuronic acid building blocks. High-resolution infrared spectra of a systematic set of synthetic heparan sulfate stereoisomers were recorded in the fingerprint region from 1000 to 1800 cm–1. The experiments reveal a characteristic combination of spectral features for each of the four diastereomers studied and imply structural modularity in the vibrational fingerprints. Strong spectrum-structure correlations were found and rationalized by state-of-the-art quantum chemical calculations. The findings demonstrate the potential of cryogenic infrared spectroscopy to extend the mass spectrometry-based toolkit for the sequencing of heparan sulfate and structurally related biomolecules.

Citation

Lettow, M., Grabarics, M., Greis, K., Mucha, E., Thomas, D. A., Chopra, P., Boons, G.-J., Karlsson, R., Turnbull, J. E., Meijer, G., Miller, R. L., von Helden, G., & Pagel, K. (2020). Cryogenic Infrared Spectroscopy Reveals Structural Modularity in the Vibrational Fingerprints of Heparan Sulfate Diastereomers. Analytical Chemistry, 92(15), 10228-10232. https://doi.org/10.1021/acs.analchem.0c02048

• Journal Article Type: Article
• Online Publication Date: Jul 13, 2020
• Publication Date: Aug 4, 2020
• Deposit Date: May 30, 2023
• Journal: Analytical Chemistry
• Print ISSN: 0003-2700
• Electronic ISSN: 1520-6882
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 92
• Issue: 15
• Pages: 10228-10232
• DOI: https://doi.org/10.1021/acs.analchem.0c02048
• Keywords: Analytical Chemistry
• Public URL: https://keele-repository.worktribe.com/output/429048