期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 129, 期 24, 页码 7690-7701出版社
AMER CHEMICAL SOC
DOI: 10.1021/ja0708971
关键词
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资金
- NIGMS NIH HHS [R37 GM044154-17, R37 GM044154] Funding Source: Medline
Sugar-assisted ligation (SAL) presents an attractive strategy for the synthesis of glycopeptides, including the synthesis of cysteine-free beta-O-linked and N-linked glycopeptides. Here we extended the utility of SAL for the synthesis of alpha-O-linked glycopeptides and glycoproteins. In order to explore SAL in the context of glycoprotein synthesis, we developed a new chemical synthetic route for the alpha-O-linked glycoprotein diptericin epsilon. In the first stage of our synthesis, diptericin segment Cys(Acm)(37)-Gly(52) and segment Val(53)-Phe(82) were assembled by SAL through a Gly-Val ligation junction. Subsequently, after Acm deprotection, diptericin segment Cys(37)-Phe(82) was ligated to segment Asp(1)-Asn(36) by means of native chemical ligation (NCL) to give the full sequence of diptericin epsilon. In the final synthetic step, hydrogenolysis was applied to remove the thiol handle from the sugar moiety with the concomitant conversion of mutated Cys(37) into the native alanine residue. In addition, we extended the applicability of SAL to the synthesis of glycopeptides containing cysteine residues by carrying out selective desulfurization of the sulfhydryl-modified sugar moiety in the presence of acetamidomethyl (Acm) protected cysteine residues. The results presented here demonstrated for the first time that SAL could be a general and useful tool in the chemical synthesis of glycoproteins.
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