Title : Other O-glycoprotomic Studies on Complex Biofluids
Abstract :
- In the recent past efforts have been made to investigate the O-glycoproteome of different complex biological samples
- Halim et al., for instance, analyzed the O-glycoproteome of cerebrospinal fluid ( CSF ) using a sialic-acid capture-and-release protocol (30)
- This protocol is based on the sialic acid specific hydrazide capturing of periodate oxidized glycoproteins
- Upon tryptic digestion the protocol allows the acid hydrolysis of sialic acid glycosidic bonds in order to release and analyze (formerly) sialylated glycopeptides
- To focus on O-glycosylations the authors included a peptide N-glycosidase F ( PNGase F) sample pretreatment step to remove N-glycans
- The authors have used an automated CID-MS2 /-MS3 spectra search protocol for glycopeptide identification (Peptide-GalNAc-Gal) and have employed ECD and ETD to pinpoint the glycosylation sites
- In total they have identified 106 O-glycosylation sites and could pinpoint 67 of these
- The identified CSF O-glycopeptides belong to 49 different proteins and were predominately decorated with structures corresponding to core-1 mucin-type O-glycans
- In a previous study the same group has also investigated the human urinary N-and O-glycoproteome using the sialic-acid capture-and-release protocol (58)
- Unfortunately, the applied protocol does not allow the enrichment of nonsialylated glycoproteins nor does it give any information on the degree of sialylation of the attached O-glycan moieties
- This limits the applicability of this procedure, as the degree of O-glycan sialylation is a crucial determinant in the pathogenesis of a number of diseases (22)
- In another large-scale glycoproteomics study conducted by Hägglund et al. in 2007 human plasma proteins , derived from Cohn fraction IV of a plasma fractionation, were analyzed with respect to occupied N- and O-glycosylation sites (60)
- The analyzed Cohn fraction is supposed to contain mainly α-globulins, like plasminogen and haptoglobin , and is depleted from γ-globulins and serum albumin
- The authors have employed two different enzymatic deglycosylation strategies to pinpoint occupied N-glycosylation sites : ( 1) PNGase F + H218O; (2) endo-β-N-acetylglucosaminidases (Endo D and Endo H) + different exoglycosidases
- These two strategies were applied on HILIC enriched tryptic (glyco) peptides , that were fractionated by strong cation exchange chromatography and eventually measured by LC- ESI-MS/MS using high-energy CID
- The authors were able to identify 103 N-glycosylation sites as well as 23 O-glycosylation sites/regions derived from 61 and 11 human blood plasma proteins , respectively
- Unfortunately, the occupied O-glycosylation sites could not be pinpointed and no information on the glycan moiety could be deduced
- In 2012 Darula et al. reported on the O-glycoproteomic analysis of bovine serum (77)
- In this study the authors have combined different protein- and peptide-level prefractionation and enrichment strategies, including jacalin lectin affinity chromatography, mixed-mode chromatography, and electrostatic repulsion hydrophilic interaction chromatography (ERLIC) to enrich tryptic mucin-type O-glycopeptides
- After additional use of exoglycosidases to improve glycopeptide characterization, truncated glycopeptides were subjected to LC- ESI-MS/MS with HCD and ETD for automated peptide identification and glycosylation site determination
- Overall, the authors could identify and pinpoint 124 glycosylation sites in 51 proteins , including many O-glycosylation sites that have not been described before—unfortunately, though, at the expense of the intact glycan structure
- In a recent publication from Bai et al. an analytical workflow is presented, which allows the mapping of mucin-type O-glycosylation sites on glycoproteins present in human blood plasma (76)
- The authors have used jacalin lectin affinity chromatography to enriched tryptic O-glycopeptides (peptide\+GalNAc) which were treated with PNGase F and different exoglycosidases
- In this study 49 O-glycopeptides , belonging to 36 human blood plasma glycoproteins , were identified by LC- ESI-MS/MS (CID)
- Overall, the authors could assign 13 O-glycosylation sites unambiguously, of which nine sites have not been described before
Output (sent_index, trigger,
protein,
sugar,
site):
- 10. glycoproteins, , glycoproteins, -, -
- 10. nonsialylated, , glycoproteins, -, -
- 12. N-, , -, -, sites
- 14. N-glycosylation, , -, -, sites
- 16. N-glycosylation, , -, -, sites
- 17. O-glycosylation, , -, -, sites
- 19. O-glycopeptides, , -, -, O-glycopeptides
- 20. glycopeptide, , -, -, glycopeptide
- 20. glycopeptides, , -, -, glycopeptides
- 20. glycosylation, , -, -, site
- 21. O-glycosylation, , -, -, sites
- 21. glycosylation, , -, -, sites
- 22. O-glycosylation, , -, -, sites
- 22. glycoproteins, , glycoproteins, -, -
- 23. O-glycopeptides, , -, -, O-glycopeptides
- 24. O-glycopeptides, , -, -, O-glycopeptides
- 24. glycoproteins, , glycoproteins, -, -
- 25. O-glycosylation, , -, -, sites
- 3. glycoproteins, , glycoproteins, -, -
- 4. glycopeptides, , -, -, glycopeptides
- 4. sialylated, , -, -, glycopeptides
- 6. glycopeptide, , -, -, glycopeptide
- 6. glycosylation, , -, -, sites
- 7. O-glycosylation, , -, -, sites
- 8. O-glycopeptides, , -, -, O-glycopeptides
Output(Part-Of) (sent_index,
protein,
site):
- 21. proteins, sites
- 22. glycoproteins, sites
- 8. CSF, O-glycopeptides
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):