Natural Glycoforms of Human Interleukin 6 Show Atypical Plasma Clearance

Abstract

Alibrary 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.N ine IL-6 glycoforms were synthesized,s even of which were evaluated for in vivo plasma clearance in rats and compared to nonglycosylated 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

Semisynthesis of homogeneous spike RBD glycoforms from SARS-CoV-2 for profiling the correlations between glycan composition and function

“…2A , details in Supporting Information, page S10 ) [ 32 ]. Enzymatic sialylation of glycopeptide 9 [ 15 ] in the presence of recombinant α-2,3-sialyltransferase PmST3 from Pasteurella multocida [ 33 ] led to rapid generation of α-2,3-sialylated glycopeptide 10 with 83% isolated yield (Fig. 2B ).…”

“…Preparation of sialylated glycopeptide (C336–K378) commenced with synthesis of the protected peptide 15 in which Boc-hydrazide was induced to prevent undesired conjugation during subsequent HATU-assisted aspartylation. Generation of glycopeptide 16 was achieved through pseudoproline-mediated one-flask aspartylation [ 33 , 37 , 38 ]. Coupling of the carboxylic acid at D343 with glycosyl amine 7 produced 16 with a 49% isolated yield.…”

Hypoglycemic Activity of Rice Resistant-Starch Metabolites: A Mechanistic Network Pharmacology and In Vitro Approach

“…Molecular docking was verified using AutoDock Vina software to simulate the process of the regulation of T2DM by RRS metabolites through key targets. Specific information and sources on the proteins obtained in the PDB database are shown in Table S2 [ [36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51]. The results of molecular docking were evaluated based on the binding free energies, and lower binding free energies represent a better binding ability of the ligand and receptor.…”

Recent Advances in Glycopeptide and Glycoprotein Synthesis: A Refined Synthetic Probe towards the Biological World

“…A systematic study was carried out with a representative set of IL‐6 glycoforms, including complex‐type and oligomannosidic N‐glycans. [ 75 ] The chemoenzymatic semisynthesis of the library of IL‐6 glycoforms involved three segments, [ 76 ] where the short glycopeptide segment was synthesized via pseudoproline‐assisted convergent aspartylation; the N‐terminal and C‐terminal segments were obtained recombinantly from the corresponding fusion protein (Figure 11). Moreover, the sialylated glycopeptides were obtained by enzymatic sialylation using the bacterial sialyltransferases Pd2,6ST or PmST3 and purified by RP‐HPLC.…”