Traceless ?-mercaptan-assisted activation of valinyl benzimidazolinones in peptide ligations.

ABSTRACT: Peptidyl thioesters or their surrogates with C-terminal ?-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 ?-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 ?-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 ?-LPH and hPTH analogues, based on a kinetically controlled one-pot three-segment ligation and desulfurization strategy.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC5892131 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature