How General Is Anomeric Retention during Collision-Induced Dissociation of Glycans?

Abstract

Despite the essential role that glycans play in many biological processes, their isomeric complexity makes their structural determination particularly challenging. Tandem mass spectrometry has played a central role in glycan analysis, and recent work has shown that fragments generated by collision-induced dissociation (CID) of disaccharides can retain the anomeric configuration of the glycosidic bond. If this result proves to be general, it would provide a powerful new tool for glycan sequencing. In this work, we use messenger-tagging infrared (IR) spectroscopy to investigate the generality of anomer retention in CID by exploring different fragmentation channels in glycans of increasing complexity. Our results demonstrate that anomericity seems to be retained irrespective of fragment size and branching.

Applications of infrared spectroscopy in polysaccharide structural analysis: Progress, challenge and perspective

“…With this ultrahigh resolution, characteristic fingerprints for a series of larger carbohydrates, ranging from heptasaccharide to decasaccharide, were provided ( Yalovenko, Yatsyna, Bansal, AbiKhodr, & Rizzo, 2020 ). The generality of anomeric retention during CID of carbohydrates was also investigated by cryogenic IR-MS conducted by Pellegrinelli et al (2020) . They validated the finding of Schindler et al (2017b) and extended it from disaccharides to hexasaccharides, demonstrating that anomeric memory can be retained irrespective of fragment size and branching.…”

Analyzing glycans cleaved from a biotherapeutic protein using ultrahigh-resolution ion mobility spectrometry together with cryogenic ion spectroscopy

“…6,[10][11][12][13][14][15][16][17] Recently, spectroscopy-based methods have been combined with MS to tackle the issue of glycan identification. [18][19][20][21][22][23][24][25][26][27][28] For relatively large and complex molecules such as N-linked glycans, cryogenic spectroscopy is best suited to distinguishing the subtle structural differences between isomers. [21][22][23][24][25][26][27][28][29] Because vibrational spectra reflect intrinsic molecular properties of a molecule, they are insensitive to the range of experimental conditions that might be encountered in different laboratories.…”

“…[18][19][20][21][22][23][24][25][26][27][28] For relatively large and complex molecules such as N-linked glycans, cryogenic spectroscopy is best suited to distinguishing the subtle structural differences between isomers. [21][22][23][24][25][26][27][28][29] Because vibrational spectra reflect intrinsic molecular properties of a molecule, they are insensitive to the range of experimental conditions that might be encountered in different laboratories. 26 In this work, we combine ultrahigh-resolution ion mobility spectrometry and cryogenic, vibrational spectroscopy to analyze four of the N-glycans released from the therapeutic protein etanercept, which is a key pharmaceutical component of the drug Enbrel™.…”

Unravelling the structures of sodiated β-cyclodextrin and its fragments

“…[36][37][38][39] In a very recent study we have been able to identify anomeric CID fragments from single glycans by their IR spectra. 40 The advantage of measuring spectra of cryogenically cooled ions is that it greatly reduces thermal inhomogeneous broadening, resulting in significantly enhanced spectral resolution, which is particularly important for the analysis of large molecules possessing inherently congested spectra. 33 Here we investigate the CID products of sodiated β-CD using cryogenic IR spectroscopy.…”