Title : Novel
Asn-linked oligosaccharides terminating in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.
Abstract :
- are present in recombinant human protein C expressed in human kidney 293 cells
- Recombinant human Protein C ( rHPC ), expressed in human kidney 293 cells, has a higher anticoagulant activity than plasma HPC , while its in vivo circulatory half-life is essentially unaltered compared to that of the natural protein
- In seeking to elucidate the molecular basis for the improved efficacy of the recombinant antithrombotic drug, we focused on the carbohydrate moiety of rHPC
- Protein C is a heavily post-translationally modified serine protease with four N-glycosylation sites
- Glycosyl com position analysis of rHPC revealed a 5-fold higher fucose content and a 2-fold lower sialic acid content compared to plasma HPC
- In addition, we found that rHPC contains N-acetylgalactosamine (2.6 mol GalNAc/mol rHPC) in its Asn-linked oligosaccharides, while plasma HPC is devoid of GalNAc
- The Asn-linked oligosaccharides of rHPC were released by N-glycanase and separated into 25 fractions by high-pH anion-exchange chromatography
- The most abundant oligosaccharides were structurally characterized by glycosyl com position and linkage analysis, in conjunction with 1H-NMR spectroscopy at 600 MHz
- The structure of the major neutral oligosaccharide in rHPC was determined to be: [formula: see text] Two representatives of the sialylated oligosaccharides in rHPC are: [formula: see text] and [formula: see text] Thus, many of the Asn-linked oligosaccharides in rHPC were found to terminate in GalNAc beta (1-->4)GlcNAc beta (1-->.
- , in NeuAc alpha (2-->6)GalNAc beta (1-->4)GlcNAc beta (1-->.
- , and/or in GalNAc beta (1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.
-
- Since the latter trisaccharide was first [Yan, S.B., Chao, B.Y. and Van Halbeek,H. (1992) J. Cell
- Biochem., 16D, 151] observed in the Asn-linked oligosaccharides of rHPC derived from human kidney 293 cells, we propose to label the GalNAc beta-(1-->4)[Fuc alpha (1-->3)]GlcNAc beta (1-->.
- terminal trisaccharide the PC-293 determinant
- The PC-293-containing oligosaccharides may contribute to the higher anticoagulant activity of rHPC as compared to plasma HPC
Output (sent_index, trigger,
protein,
sugar,
site):
- 0. Asn-linked, , -, Novel Asn-linked oligosaccharides, Asn
- 13. Asn-linked, , -, the Asn-linked oligosaccharides, Asn
- 13. rHPC, , rHPC, the Asn-linked oligosaccharides, -
- 3. rHPC, , rHPC, the carbohydrate moiety, -
- 4. N-glycosylation, , -, -, sites
- 6. Asn-linked, , -, its Asn-linked oligosaccharides, Asn
- 6. contains, , rHPC, 2.6 mol GalNAc/mol rHPC, -
- 6. contains, , rHPC, N-acetylgalactosamine, -
- 7. Asn-linked, , -, The Asn-linked oligosaccharides, Asn
- 7. rHPC, , rHPC, The Asn-linked oligosaccharides, -
- 9. Asn-linked, , -, the Asn-linked oligosaccharides, Asn
- 9. oligosaccharide, , rHPC, oligosaccharide, -
- 9. oligosaccharides, , rHPC, oligosaccharides, -
- 9. sialylated, , -, the sialylated oligosaccharides, -
Output(Part-Of) (sent_index,
protein,
site):
*Output_Site_Fusion* (sent_index,
protein,
sugar,
site):