ORCID Profile
0000-0002-2550-637X
Current Organisation
University of Oxford
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Publisher: Springer Science and Business Media LLC
Date: 20-03-2020
DOI: 10.1038/S41467-020-15284-Y
Abstract: Despite evident regulatory roles of heparan sulfate (HS) saccharides in numerous biological processes, definitive information on the bioactive sequences of these polymers is lacking, with only a handful of natural structures sequenced to date. Here, we develop a “ S hotgun” I on M obility M ass S pectrometry S equencing (SIMMS 2 ) method in which intact HS saccharides are dissociated in an ion mobility mass spectrometer and collision cross section values of fragments measured. Matching of data for intact and fragment ions against known values for 36 fully defined HS saccharide structures (from di- to decasaccharides) permits unambiguous sequence determination of validated standards and unknown natural saccharides, notably including variants with 3 O -sulfate groups. SIMMS 2 analysis of two fibroblast growth factor-inhibiting hexasaccharides identified from a HS oligosaccharide library screen demonstrates that the approach allows elucidation of structure-activity relationships. SIMMS 2 thus overcomes the bottleneck for decoding the informational content of functional HS motifs which is crucial for their future biomedical exploitation.
Publisher: American Chemical Society (ACS)
Date: 13-07-2020
DOI: 10.1021/ACS.ANALCHEM.0C02048
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
Publisher: Wiley
Date: 03-06-2021
Abstract: In a previous work, we explored zone broadening and the achievable plate numbers in linear drift tube ion mobility‐mass spectrometry through developing a plate‐height model [1]. On the basis of these findings, the present theoretical study extends the model by exploring peak‐to‐peak resolution and peak capacity in ion mobility separations. The first part provides a critical overview of chromatography‐influenced resolution equations, including refinement of existing formulae. Furthermore, we present exact resolution equations for drift tube ion mobility spectrometry based on first principles. Upon implementing simple modifications, these exact formulae could be readily extended to traveling wave ion mobility separations and to cases when ion mobility spectrometry is coupled to mass spectrometry. The second part focuses on peak capacity. The well‐known assumptions of constant plate number and constant peak width form the basis of existing approximate solutions. To overcome their limitations, an exact peak capacity equation is derived for drift tube ion mobility spectrometry. This exact solution is rooted in a suitable physical model of peak broadening, accounting for the finite injection pulse and subsequent diffusional spreading. By borrowing concepts from the theoretical toolbox of chromatography, we believe that the present study will help in integrating ion mobility spectrometry into the unified language of separation science.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0AN00433B
Abstract: In analogy to chromatography, a plate-height model of drift tube ion mobility-mass spectrometry is presented that describes zone broadening and resolving power in ion mobility separations.
Publisher: American Chemical Society (ACS)
Date: 07-09-2021
Publisher: American Chemical Society (ACS)
Date: 12-05-2021
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Márkó Grabarics.