Review of ion mobility MS for glycan sequencing
Gray CJ, Thomas B, Upton R, Migas LG, Eyers CE, Barran PE, Flitsch SL. (2016) Applications of ion mobility mass spectrometry for high throughput, high
resolution glycan analysis.. Biochim Biophys Acta. 2016 Feb 22. pii: S0304-4165(16)30016-2. doi: 10.1016/j.bbagen.2016.02.003
BACKGROUND: Diverse varieties of often heterogeneous glycans are ubiquitous in
nature. They play critical roles in recognition events, act as energy stores and
provide structural stability at both molecular and cellular levels. Technologies
capable of fully elucidating the structures of glycans are far behind the other
'-omic' fields. Liquid chromatography (LC) and mass spectrometry (MS) are
currently the most useful techniques for high-throughput analysis of glycans.
However, these techniques do not provide full unambiguous structural information
and instead the gap in full sequence assignment is frequently filled by a priori
knowledge of the biosynthetic pathways and the assumption that these pathways are
highly conserved.
SCOPE OF THE REVIEW: This comprehensive review details the rise of the emerging
analytical technique ion mobility spectrometry (IMS) (coupled to MS) to
facilitate the determination of three-dimensional shape: the separation and
characterization of isobaric glycans, glyco(peptides/proteins), glycolipids,
glycosaminoglycans and other polysaccharides; localization of sites of
glycosylation; or interpretation of the conformational change to proteins upon
glycan binding.
MAJOR CONCLUSIONS: IMS is a highly promising new analytical route, able to
provide rapid isomeric separation (ms timescale) of either precursor or product
ions facilitating MS characterization. This additional separation also enables
the deconvolution of carbohydrate MS(/MS) information from contaminating ions,
improving sensitivity and reducing chemical noise. Derivation of collision cross
sections (CCS) from IM-MS(/MS) data and subsequent calculations validate putative
structures of carbohydrates from ab initio derived candidates. IM-MS has
demonstrated that amounts of specific glycan isomers vary between disease states,
which would be challenging to detect using standard analytical approaches.
GENERAL SIGNIFICANCE: IM-MS is a promising technique that fills an important gap
within the Glycomics toolbox, namely identifying and differentiating the
three-dimensional structure of chemically similar carbohydrates and
glycoconjugates.
resolution glycan analysis.. Biochim Biophys Acta. 2016 Feb 22. pii: S0304-4165(16)30016-2. doi: 10.1016/j.bbagen.2016.02.003
BACKGROUND: Diverse varieties of often heterogeneous glycans are ubiquitous in
nature. They play critical roles in recognition events, act as energy stores and
provide structural stability at both molecular and cellular levels. Technologies
capable of fully elucidating the structures of glycans are far behind the other
'-omic' fields. Liquid chromatography (LC) and mass spectrometry (MS) are
currently the most useful techniques for high-throughput analysis of glycans.
However, these techniques do not provide full unambiguous structural information
and instead the gap in full sequence assignment is frequently filled by a priori
knowledge of the biosynthetic pathways and the assumption that these pathways are
highly conserved.
SCOPE OF THE REVIEW: This comprehensive review details the rise of the emerging
analytical technique ion mobility spectrometry (IMS) (coupled to MS) to
facilitate the determination of three-dimensional shape: the separation and
characterization of isobaric glycans, glyco(peptides/proteins), glycolipids,
glycosaminoglycans and other polysaccharides; localization of sites of
glycosylation; or interpretation of the conformational change to proteins upon
glycan binding.
MAJOR CONCLUSIONS: IMS is a highly promising new analytical route, able to
provide rapid isomeric separation (ms timescale) of either precursor or product
ions facilitating MS characterization. This additional separation also enables
the deconvolution of carbohydrate MS(/MS) information from contaminating ions,
improving sensitivity and reducing chemical noise. Derivation of collision cross
sections (CCS) from IM-MS(/MS) data and subsequent calculations validate putative
structures of carbohydrates from ab initio derived candidates. IM-MS has
demonstrated that amounts of specific glycan isomers vary between disease states,
which would be challenging to detect using standard analytical approaches.
GENERAL SIGNIFICANCE: IM-MS is a promising technique that fills an important gap
within the Glycomics toolbox, namely identifying and differentiating the
three-dimensional structure of chemically similar carbohydrates and
glycoconjugates.