The reduction of oxidized methionine residues in peptide thioesters with NH4I-Me2S
The reduction of oxidized methionine residues in peptide thioesters with NH4I-Me2S
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DOI：
10.1039/b603543d
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发表时间：
2006-01-01
影响因子：
3.2
通讯作者：
Hackenberger, Christian P. R.
中科院分区：
文献类型：
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作者：
Hackenberger, Christian P. R.
以Me2S为助还原剂，用NH4I可将多肽硫酯中氧化的蛋氨酸残基快速还原为相应的硫化物。以28个氨基酸的多肽硫酸酯和N-末端蛋氨酸氧化物为模型体系的对比还原研究揭示了Me2S加成对于避免活性硫酸酯官能团的水解的重要性。此外，含有NH4I-Me2S的裂解鸡尾酒已被用于各种硫代酯的全球脱保护，没有显示出水解或氧化副产物。这些结果证明了亚砜作为保护基在先进的多肽合成技术中的普遍适用性，因为它促进了用于天然化学连接(NCL)的含有蛋氨酸的多肽硫酯的制备和处理。
Oxidized methionine residues in peptide thioesters can be reduced rapidly with NH4I to the corresponding sulfide by using Me2S as coreductant. Comparative reduction studies employing a 28-amino acid peptide thioester with an N-terminal methionine oxide as model system revealed the importance of the Me2S addition to avoid hydrolysis of the reactive thioester functionality. In addition, an NH4I - Me2S containing cleavage cocktail has been used for the global deprotection of various thioesters which revealed no hydrolysis or oxidative side products. These results demonstrate the general applicability of sulfoxides as protecting groups in advanced peptide synthesis techniques by facilitating the preparation and handling of methionine containing peptide thioesters for native chemical ligation (NCL).