Traceless β-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations. Issue 7 (22nd January 2018)

• Record Type: Journal Article
• Authors: Wang, Yinglu; Han, Lin; Yuan, Ning; Wang, Hanxuan; Li, Hongxing; Liu, Jinrong; Chen, Huan; Zhang, Qiang; Dong, Suwei
• Is Part Of: Chemical science. Volume 9:Issue 7(2018)
• Page Start: 1940
• Page End: 1946
• Publication Date: 2018-01-22
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c7sc04148a
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : An internal activation strategy-enabled traceless ligation at sterically hindered Val-Xaa site is accomplished under thiol additive-free conditions assisted by a β-mercaptan on the C-terminal valine residue. Abstract : 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.