Natural Glycoforms of Human Interleukin 6 Show Atypical Plasma Clearance.

Animals Cell Line Cell Proliferation / drug effects Chromatography, High Pressure Liquid Galactose / metabolism Glycopeptides / blood Glycosylation Humans Interleukin-6 / blood Mice N-Acetylneuraminic Acid / metabolism Rats Recombinant Fusion Proteins / biosynthesis Spectrometry, Mass, Electrospray Ionization
glycopeptides glycoproteins native chemical ligation oligosaccharides serum clearance

Journal

Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543

Informations de publication

Date de publication:
07 06 2021
Historique:
received: 31 01 2021
pubmed: 24 3 2021
medline: 7 9 2021
entrez: 23 3 2021
Statut: ppublish

Résumé

A library of glycoforms of human interleukin 6 (IL-6) comprising complex and mannosidic N-glycans was generated by semisynthesis. The three segments were connected by sequential native chemical ligation followed by two-step refolding. The central glycopeptide segments were assembled by pseudoproline-assisted Lansbury aspartylation and subsequent enzymatic elongation of complex N-glycans. Nine IL-6 glycoforms were synthesized, seven of which were evaluated for in vivo plasma clearance in rats and compared to non-glycosylated recombinant IL-6 from E. coli. Each IL-6 glycoform was tested in three animals and reproducibly showed individual serum clearances depending on the structure of the N-glycan. The clearance rates were atypical, since the 2,6-sialylated glycoforms of IL-6 cleared faster than the corresponding asialo IL-6 with terminal galactoses. Compared to non-glycosylated IL-6 the plasma clearance of IL-6 glycoforms was delayed in the presence of larger and multibranched N-glycans in most cases.

Identifiants

DOI: 10.1002/anie.202101496 PMID: 33756033 PMC: PMC8251587
pubmed: 33756033
doi: 10.1002/anie.202101496
pmc: PMC8251587
doi:

Substances chimiques

Glycopeptides 0
Interleukin-6 0
Recombinant Fusion Proteins 0
N-Acetylneuraminic Acid GZP2782OP0
Galactose X2RN3Q8DNE

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

13380-13387

Informations de copyright

© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

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Auteurs

Andreas Reif (A)

Bioorganic Chemistry, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.

Kevin Lam (K)

Bioorganic Chemistry, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.

Sascha Weidler (S)

Bioorganic Chemistry, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.

Marie Lott (M)

Bioorganic Chemistry, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.

Irene Boos (I)

Bioorganic Chemistry, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.

Juliane Lokau (J)

Department of Pathology, Medical Faculty, Otto von Guericke University Magdeburg, 39120, Magdeburg, Germany.

Christian Bretscher (C)

Department of Biochemistry, Kiel University, 24098, Kiel, Germany.

Manuel Mönnich (M)

Bioorganic Chemistry, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.

Lukas Perkams (L)

Bioorganic Chemistry, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.

Marina Schmälzlein (M)

Bioorganic Chemistry, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.

Christopher Graf (C)

Bioorganic Chemistry, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.

Jan-Patrick Fischer (JP)

Bioorganic Chemistry, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.

Carolin Lechner (C)

Bioorganic Chemistry, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.

Kerstin Hallstein (K)

Protein Engineering & Antibody Technologies, Merck Healthcare KGaA, Frankfurter Str. 250, 64293, Darmstadt, Germany.

Stefan Becker (S)

Protein Engineering & Antibody Technologies, Merck Healthcare KGaA, Frankfurter Str. 250, 64293, Darmstadt, Germany.

Michael Weyand (M)

Department of Biochemistry, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.

Clemens Steegborn (C)

Department of Biochemistry, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.

Gerhard Schultheiss (G)

Animal Welfare, Kiel University, 24098, Kiel, Germany.

Stefan Rose-John (S)

Department of Biochemistry, Kiel University, 24098, Kiel, Germany.

Christoph Garbers (C)

Department of Pathology, Medical Faculty, Otto von Guericke University Magdeburg, 39120, Magdeburg, Germany.

Carlo Unverzagt (C)

Bioorganic Chemistry, University of Bayreuth, Universitätsstraße 30, 95447, Bayreuth, Germany.
ORCID: 0000-0001-6492-1747

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Natural Glycoforms of Human Interleukin 6 Show...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Natural Glycoforms of Human Interleukin 6 Show...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Natural Glycoforms of Human Interleukin 6 Show...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Chromatographie › Chromatographie en phase liquide › Chromatographie en phase liquide à haute performance › Natural Glycoforms of Human Interleukin 6 Show...
questionsmedicales.fr › Glucides › Sucres › Oses › Hexose › Galactose › Natural Glycoforms of Human Interleukin 6 Show...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Glycopeptides › Natural Glycoforms of Human Interleukin 6 Show...
questionsmedicales.fr › Métabolisme › Métabolisme glucidique › Glycosylation › Natural Glycoforms of Human Interleukin 6 Show...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Natural Glycoforms of Human Interleukin 6 Show...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-6 › Natural Glycoforms of Human Interleukin 6 Show...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Natural Glycoforms of Human Interleukin 6 Show...
questionsmedicales.fr › Glucides › Oses acides › Acides neuraminiques › Acides sialiques › Acide N-acétyl-neuraminique › Natural Glycoforms of Human Interleukin 6 Show...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Natural Glycoforms of Human Interleukin 6 Show...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines recombinantes › Protéines de fusion recombinantes › Natural Glycoforms of Human Interleukin 6 Show...
questionsmedicales.fr › Techniques d'investigation › Techniques de chimie analytique › Spectrométrie de masse › Spectrométrie de masse ESI › Natural Glycoforms of Human Interleukin 6 Show...