Synthesis of glycosylated human interleukin-1α, neoglyco IL-1α, coupled with N-acetylneuraminic acid

Abstract

In order to develop glycosylated cytokine, recombinant human IL-1α was chemically modified with N-acetylneuraminic acid (NANA). NANA with C9 spacer, 8-(hydrazinocarbonyl)octyl 5-acetamido-3, 5-dideoxy-D-glycero-α-D-galacto-2-nonulo-pyranosidonic acid potassium salt (6), was synthesized by glycosylation of C9 spacer, 8-[2-N-(benzyloxycarbonyl)hydrazinocarbonyl]octanol, with methylthio glycoside derivatives of NANA in the presence of molecular sieves 3Å and methyl(methylthio)sulfonium trifrate in propionitrile, followed by separation of α and β anomers with a column chromatography and deprotection. Compound 6 was coupled to IL-1α by the acyl azide method. The glycosylated IL-1 was purified by anion-exchange chromatography, and NANA coupled to IL-1 was confirmed by oxidation with NalO4−. Based on the molecular weight average number of carbohydrate molecules introduced per molecule of IL-1α was estimated to be 2.9.

DOI: 10.1023/A:1007017920392

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Cite this paper

@article{Chiba2004SynthesisOG, title={Synthesis of glycosylated human interleukin-1α, neoglyco IL-1α, coupled with N-acetylneuraminic acid}, author={Taku Chiba and Kayoko Moriya and Sachi Nabeshima and Hidetoshi Hayashi and Yutaka Kobayashi and Satoshi Sasayama and Kikuo Onozaki}, journal={Glycoconjugate Journal}, year={2004}, volume={16}, pages={499-505} }