Synthesis of Maleimide-Activated Carbohydrates as Chemoselective Tags for Site-Specific Glycosylation of Peptides and Proteins

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• 作者：Jiahong Ni ; Suddham Singh ; and Lai-Xi Wang
• 刊名：Bioconjugate Chemistry
• 出版年：2003
• 出版时间：January 2003
• 年：2003
• 卷：14
• 期：1
• 页码：232 - 238
• 全文大小：141K
• 年卷期：v.14,no.1(January 2003)
• ISSN：1520-4812

文摘

An array of maleimide-activated mono- and oligosaccharides were synthesized to permit site-specificglycosylation of cysteine-containing peptides and proteins. Maleimide-activated monosaccharides, inwhich the native - or -O-glycosidic linkages found for nonreducing terminal sugars of nativeglycoproteins are preserved, were prepared using 2'-aminoethyl glycosides as the key intermediates.In addition, a native high-mannose type oligosaccharide, Man₉GlcNAc₂Asn, was converted into itsmaleimide-activated form by taking advantage of the existing amino group in the Asn portion. Theapplication of these maleimide-activated carbohydrates was exemplified by the site-specific glycosylation of a 36-mer HIV-1 gp41 peptide, T20, which is a potent inhibitor against HIV infection. Thechemoselective ligation was found to be rapid, highly efficient, and essentially quantitative. Taggingthe biologically active peptide with a mannose and/or oligomannose moiety will be useful for targetingthe drug to macrophage and dendritic cells, which are primary targets for HIV-1 infection and areexpressing mannose- and oligomanose-specific receptors on their surface. In combination with site-specific mutagenesis, the maleimide-activated carbohydrates can serve as generally applicable tagsfor site-specific glycosylation of proteins via the highly efficient maleimide-thiol ligation reaction.