Benefits of Chemical Sugar Modifications Introduced by Click Chemistry for Glycoproteomic Analyses.
J Am Soc Mass Spectrom
; 32(9): 2366-2375, 2021 Sep 01.
Article
en En
| MEDLINE
| ID: mdl-33871988
ABSTRACT
Mucin-type O-glycosylation is among the most complex post-translational modifications. Despite mediating many physiological processes, O-glycosylation remains understudied compared to other modifications, simply because the right analytical tools are lacking. In particular, analysis of intact O-glycopeptides by mass spectrometry is challenging for several reasons; O-glycosylation lacks a consensus motif, glycopeptides have low charge density which impairs ETD fragmentation, and the glycan structures modifying the peptides are unpredictable. Recently, we introduced chemically modified monosaccharide analogues that allowed selective tracking and characterization of mucin-type O-glycans after bioorthogonal derivatization with biotin-based enrichment handles. In doing so, we realized that the chemical modifications used in these studies have additional benefits that allow for improved analysis by tandem mass spectrometry. In this work, we built on this discovery by generating a series of new GalNAc analogue glycopeptides. We characterized the mass spectrometric signatures of these modified glycopeptides and their signature residues left by bioorthogonal reporter reagents. Our data indicate that chemical methods for glycopeptide profiling offer opportunities to optimize attributes such as increased charge state, higher charge density, and predictable fragmentation behavior.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Glicopéptidos
/
Azúcares
/
Química Clic
Idioma:
En
Revista:
J Am Soc Mass Spectrom
Año:
2021
Tipo del documento:
Article