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., …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