4. Traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations
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作者:Yinglu Wang, Lin Han, Ning Yuan, Hanxuan Wang, Hongxing Li, Jinrong Liu, Huan Chen, Qiang Zhang* and Suwei Dong*
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发布时间: 2018-06-05
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1311 次浏览
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Chem. Sci. 2018, 9, 1940.
Yinglu Wang, Lin Han, Ning Yuan, Hanxuan Wang, Hongxing Li, Jinrong Liu, Huan Chen, Qiang Zhang* and Suwei Dong*
Peptidyl thioesters or their surrogates with C-terminal β-branched hydrophobic amino acid residues usually exhibit poor reactivities in ligation reactions. Thus, activation using exogenous additives is required to ensure an acceptable reaction efficiency. Herein, we report a traceless ligation at Val-Xaa sites under mild thiol additive-free reaction conditions, whereby the introduction of β-mercaptan on the C-terminal valine residue effectively activates the otherwise unreactive N-acyl-benzimidazolinone (Nbz), and enables the use of a one-pot ligation–desulfurization strategy to generate the desired peptide products. The orthogonality between β-thiovaline-Nbz and a conventional alkyl thioester, as well as the convenient access to the former from readily available penicillamine, also allowed expedited assembly of the peptidic hormone β-LPH and hPTH analogues, based on a kinetically controlled one-pot three-segment ligation and desulfurization strategy.
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