2 research outputs found
Natural Glycoforms of Human Interleukin 6 show atypical plasma clearance
A library of glycoforms of human interleukin 6 (ILâ6) comprising complex and mannosidic Nâglycans was generated by semisynthesis. The three segments were connected by sequential native chemical ligation followed by twoâstep refolding. The central glycopeptide segments were assembled by pseudoprolineâassisted Lansbury aspartylation and subsequent enzymatic elongation of complex Nâglycans. Nine ILâ6 glycoforms were synthesized, seven of which were evaluated for in vivo plasma clearance in rats and compared to nonâglycosylated recombinant ILâ6 from E. coli. Each ILâ6 glycoform was tested in three animals and reproducibly showed individual serum clearances depending on the structure of the Nâglycan. The clearance rates were atypical, since the 2,6âsialylated glycoforms of ILâ6 cleared faster than the corresponding asialo ILâ6 with terminal galactoses. Compared to nonâglycosylated ILâ6 the plasma clearance of ILâ6 glycoforms was delayed in the presence of larger and multibranched Nâglycans in most case
Natural Glycoforms of Human Interleukin 6 Show Atypical Plasma Clearance
A library of glycoforms of human interleukin 6 (ILâ6) comprising complex and mannosidic Nâglycans was generated by semisynthesis. The three segments were connected by sequential native chemical ligation followed by twoâstep refolding. The central glycopeptide segments were assembled by pseudoprolineâassisted Lansbury aspartylation and subsequent enzymatic elongation of complex Nâglycans. Nine ILâ6 glycoforms were synthesized, seven of which were evaluated for in vivo plasma clearance in rats and compared to nonâglycosylated recombinant ILâ6 from E. coli. Each ILâ6 glycoform was tested in three animals and reproducibly showed individual serum clearances depending on the structure of the Nâglycan. The clearance rates were atypical, since the 2,6âsialylated glycoforms of ILâ6 cleared faster than the corresponding asialo ILâ6 with terminal galactoses. Compared to nonâglycosylated ILâ6 the plasma clearance of ILâ6 glycoforms was delayed in the presence of larger and multibranched Nâglycans in most case