The essential role of the sialic acid residues for IFN-β1a activity determined in vivo

Lasse Dissing Olesen, Morten Thaysen Andersen

Publikation: Konferencebidrag uden forlag/tidsskriftPosterForskning

Resumé

 
OriginalsprogEngelsk
Publikationsdato2008
StatusUdgivet - 2008
BegivenhedSialoGlyco Conference 2008 - Moskva, Skt. Petersborg, Rusland
Varighed: 21. jul. 200826. jul. 2008

Konference

KonferenceSialoGlyco Conference 2008
LandRusland
ByMoskva, Skt. Petersborg
Periode21/07/200826/07/2008

Fingeraftryk

N-Acetylneuraminic Acid
Congenic Mice
Relapsing-Remitting Multiple Sclerosis
Messenger RNA
Glycoside Hydrolases
Orthomyxoviridae
Glycosylation

Citer dette

Olesen, L. D., & Andersen, M. T. (2008). The essential role of the sialic acid residues for IFN-β1a activity determined in vivo. Poster session præsenteret på SialoGlyco Conference 2008, Moskva, Skt. Petersborg, Rusland.
Olesen, Lasse Dissing ; Andersen, Morten Thaysen. / The essential role of the sialic acid residues for IFN-β1a activity determined in vivo. Poster session præsenteret på SialoGlyco Conference 2008, Moskva, Skt. Petersborg, Rusland.
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title = "The essential role of the sialic acid residues for IFN-β1a activity determined in vivo",
abstract = "  Recombinant human interferon-beta (rhIFN-β) is the leading therapeutic intervention shown to change the cause of relapsing remitting multiple sclerosis and both a non-glycosylated and a significantly more active glycosylated variant of rhIFN-β are used in treatment. This study investigates the function of the rhIFN-β1a glycan moiety and its individual carbohydrate residues using the myxovirus resistance (Mx) mRNA as a biomarker in Mx-congenic mice. We showed that the Mx mRNA level in blood leukocytes peaked three hours after subcutaneous administration of rhIFN-β1a. In addition, a clear dose-response relationship was confirmed and the Mx response was shown to be receptor mediated. Using specific glycosidases, different glycosylation analogs of rhIFN-β1a were obtained and their activities determined. The glycosylated rhIFN-β1a showed significantly higher activity than its deglycosylated counterpart, due to a protein stabilization/solubilization effect of the glycan. Interestingly, the terminating sialic acids were essential for these effects. Conclusively, the structure/bioactivity relationship of rhIFN-β1a was determined in vivo and provided a novel insight into the role of the rhIFN-β1a glycan and its carbohydrate residues. The possibilities of improving the pharmacological properties of rhIFN-β1a using glycoengineering are discussed.",
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author = "Olesen, {Lasse Dissing} and Andersen, {Morten Thaysen}",
year = "2008",
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Olesen, LD & Andersen, MT 2008, 'The essential role of the sialic acid residues for IFN-β1a activity determined in vivo' SialoGlyco Conference 2008, Moskva, Skt. Petersborg, Rusland, 21/07/2008 - 26/07/2008, .

The essential role of the sialic acid residues for IFN-β1a activity determined in vivo. / Olesen, Lasse Dissing; Andersen, Morten Thaysen.

2008. Poster session præsenteret på SialoGlyco Conference 2008, Moskva, Skt. Petersborg, Rusland.

Publikation: Konferencebidrag uden forlag/tidsskriftPosterForskning

TY - CONF

T1 - The essential role of the sialic acid residues for IFN-β1a activity determined in vivo

AU - Olesen, Lasse Dissing

AU - Andersen, Morten Thaysen

PY - 2008

Y1 - 2008

N2 -   Recombinant human interferon-beta (rhIFN-β) is the leading therapeutic intervention shown to change the cause of relapsing remitting multiple sclerosis and both a non-glycosylated and a significantly more active glycosylated variant of rhIFN-β are used in treatment. This study investigates the function of the rhIFN-β1a glycan moiety and its individual carbohydrate residues using the myxovirus resistance (Mx) mRNA as a biomarker in Mx-congenic mice. We showed that the Mx mRNA level in blood leukocytes peaked three hours after subcutaneous administration of rhIFN-β1a. In addition, a clear dose-response relationship was confirmed and the Mx response was shown to be receptor mediated. Using specific glycosidases, different glycosylation analogs of rhIFN-β1a were obtained and their activities determined. The glycosylated rhIFN-β1a showed significantly higher activity than its deglycosylated counterpart, due to a protein stabilization/solubilization effect of the glycan. Interestingly, the terminating sialic acids were essential for these effects. Conclusively, the structure/bioactivity relationship of rhIFN-β1a was determined in vivo and provided a novel insight into the role of the rhIFN-β1a glycan and its carbohydrate residues. The possibilities of improving the pharmacological properties of rhIFN-β1a using glycoengineering are discussed.

AB -   Recombinant human interferon-beta (rhIFN-β) is the leading therapeutic intervention shown to change the cause of relapsing remitting multiple sclerosis and both a non-glycosylated and a significantly more active glycosylated variant of rhIFN-β are used in treatment. This study investigates the function of the rhIFN-β1a glycan moiety and its individual carbohydrate residues using the myxovirus resistance (Mx) mRNA as a biomarker in Mx-congenic mice. We showed that the Mx mRNA level in blood leukocytes peaked three hours after subcutaneous administration of rhIFN-β1a. In addition, a clear dose-response relationship was confirmed and the Mx response was shown to be receptor mediated. Using specific glycosidases, different glycosylation analogs of rhIFN-β1a were obtained and their activities determined. The glycosylated rhIFN-β1a showed significantly higher activity than its deglycosylated counterpart, due to a protein stabilization/solubilization effect of the glycan. Interestingly, the terminating sialic acids were essential for these effects. Conclusively, the structure/bioactivity relationship of rhIFN-β1a was determined in vivo and provided a novel insight into the role of the rhIFN-β1a glycan and its carbohydrate residues. The possibilities of improving the pharmacological properties of rhIFN-β1a using glycoengineering are discussed.

KW - Glyco-engineering

KW - Interferon-beta

KW - Multiple Schlerosis

M3 - Poster

ER -

Olesen LD, Andersen MT. The essential role of the sialic acid residues for IFN-β1a activity determined in vivo. 2008. Poster session præsenteret på SialoGlyco Conference 2008, Moskva, Skt. Petersborg, Rusland.