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Publication Abstract from PubMed

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, 7 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.

Natural Glycoforms of Human Interleukin 6 show atypical plasma clearance.,Unverzagt C, Reif A, Lam K, Weidler S, Lott M, Boos I, Lokau J, Bretscher C, Monnich M, Perkams L, Schmalzlein M, Graf C, Fischer JP, Lechner C, Hallstein K, Becker S, Weyand M, Steegborn C, Schultheiss G, Rose-John S, Garbers C Angew Chem Int Ed Engl. 2021 Mar 23. doi: 10.1002/anie.202101496. PMID:33756033^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.