期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 143, 期 32, 页码 12699-12707出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.1c05567
关键词
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资金
- Walter and Eliza Hall Institute of Medical Research
- National Health and Medical Research Council of Australia (NHMRC) [GNT1139546, GNT1139549, GNT2000517]
- ARC [DP210100362]
- Australian Cancer Research Fund
- Victorian State Government Operational Infrastructure support grant
- ARC Future Fellowship
- Brian M. Davis Charitable Foundation Centenary Fellowship
Researchers have developed a novel method using Ni-catalyzed cross-coupling conditions to achieve tryptophan C-mannosylation, successfully synthesizing and studying glycopeptides. Through this method, they not only successfully identified an antibody epitope, but also completed the synthesis of an insect hormone.
The biological functions of tryptophan C-mannosylation are poorly understood, in part, due to a dearth of methods for preparing pure glycopeptides and glycoproteins with this modification. To address this issue, efficient and scalable methods are required for installing this protein modification. Here, we describe unique Ni-catalyzed cross-coupling conditions that utilize photocatalysis or a Hantzsch ester photoreductant to couple glycosyl halides with (hetero)aryl bromides, thereby enabling the alpha-C-mannosylation of 2-bromo-tryptophan, peptides thereof, and (hetero)aryl bromides more generally. We also report that 2-(alpha-D-mannopyranosyl)-L-tryptophan undergoes facile anomerization in the presence of acid: something that must be considered when preparing and handling peptides with this modification. These developments enabled the first automated solid-phase peptide syntheses of C-mannosylated glycopeptides, which we used to map the epitope of an antibody, as well as providing the first verified synthesis of Carmo-HrTH-I, a C-mannosylated insect hormone. To complement this approach, we also performed late-stage tryptophan C-mannosylation on a diverse array of peptides, demonstrating the broad scope and utility of this methodology for preparing glycopeptides.
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