Abstract
Among Dissociation Methods, Negative Electron Transfer Dissociation (NETD) Has Been Proven the Most Useful for Glycosaminoglycan (GAG) Sequencing Because It Produces Informative Fragmentation, a Low Degree of Sulfate Losses, High Sensitivity, and Translatability to Multiple Instrument Types. the Challenge, However, is to Distinguish Positional Sulfation. in Particular, NETD Has Been Reported to Fail to Differentiate 4-O- Versus 6-O-Sulfation in Chondroitin Sulfate Decasaccharide. This Raised the Concern of Whether NETD is Able to Differentiate the Rare 3-O-Sulfation from Predominant 6-O-Sulfation in Heparan Sulfate (HS) Oligosaccharides. Here, We Report that NETD Generates Highly Informative Spectra that Differentiate Sites of O-Sulfation on Glucosamine Residues, Enabling Structural Characterizations of Synthetic HS Isomers Containing 3-O-Sulfation. Further, Lyase-Resistant 3-O-Sulfated Tetrasaccharides from Natural Sources Were Successfully Sequenced. Notably, for All of the Oligosaccharides in This Study, the Successful Sequencing is based on NETD Tandem Mass Spectra of Commonly Observed Deprotonated Precursor Ions Without Derivatization or Metal Cation Adduction, Simplifying the Experimental Workflow and Data Interpretation. These Results Demonstrate the Potential of NETD as a Sensitive Analytical Tool for Detailed, High-Throughput Structural Analysis of Highly Sulfated GAGs. [Figure Not Available: See Fulltext.].
Recommended Citation
J. Wu and J. Wei and J. D. Hogan and P. Chopra and A. Joshi and W. Lu and J. Klein and G. J. Boons and C. Lin and J. Zaia, "Negative Electron Transfer Dissociation Sequencing of 3-O-Sulfation-Containing Heparan Sulfate Oligosaccharides," Journal of the American Society for Mass Spectrometry, vol. 29, no. 6, pp. 1262 - 1272, American Chemical Society, Jun 2018.
The definitive version is available at https://doi.org/10.1007/s13361-018-1907-0
Department(s)
Chemical and Biochemical Engineering
Keywords and Phrases
Fourier transform ion cyclotron resonance mass spectrometry; Glycomics; Glycosaminoglycan; Heparan sulfate; Negative electron transfer dissociation; Sulfation
International Standard Serial Number (ISSN)
1879-1123; 1044-0305
Document Type
Article - Journal
Document Version
Citation
File Type
text
Language(s)
English
Rights
© 2023 American Chemical Society, All rights reserved.
Publication Date
01 Jun 2018
PubMed ID
29564812
Comments
National Institutes of Health, Grant R21HL131554