7NXZ

Synthetic glycoform of Human Interleukin 6

This is a non-PDB format compatible entry.

Summary for 7NXZ

• Entry DOI: 10.2210/pdb7nxz/pdb
• Descriptor: Interleukin-6 (2 entities in total)
• Functional Keywords: glycosylated interleukin-6, cytokine
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 20819.73

Authors

Weyand, M.,Unverzagt, C. (deposition date: 2021-03-19, release date: 2021-04-07, Last modification date: 2024-10-23)

Primary citation

Reif, A.,Lam, K.,Weidler, S.,Lott, M.,Boos, I.,Lokau, J.,Bretscher, C.,Monnich, M.,Perkams, L.,Schmalzlein, M.,Graf, C.,Fischer, J.P.,Lechner, C.,Hallstein, K.,Becker, S.,Weyand, M.,Steegborn, C.,Schultheiss, G.,Rose-John, S.,Garbers, C.,Unverzagt, C.
Natural Glycoforms of Human Interleukin 6 Show Atypical Plasma Clearance.
Angew.Chem.Int.Ed.Engl., 60:13380-13387, 2021

PubMed Abstract: 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.

PubMed: 33756033
DOI: 10.1002/anie.202101496

Experimental method

X-RAY DIFFRACTION (1.998 Å)