P-B desulfurization: an enabling method for protein chemical synthesis and site-specific deuteration
 

P-B desulfurization: an enabling method for protein chemical synthesis and site-specific deuteration


Native chemical ligation has provided a powerful tool for protein chemical synthesis. Herein, we report an unprecedented mild system (TCEP-NaBH4 or TCEP-LiBEt3H) for chemoselective peptide desulfurization to achieve effective protein synthesis via the native chemical ligation-desulfurization approach. This method, termed P-B desulfurization, features usage of common reagents, simplicity of operation, robustness, high yielding, clean conversion and versatile functionality compatibility with complex peptides/proteins. In addition, this method allows for incorporating deuterium into the peptides after cysteine desulfurization when running the reaction in D2O buffer. Moreover, this method enables clean desulfurization for peptides carrying post-translational modifications, such as phosphorylation and crotonylation. The effectiveness of this method has been demonstrated in the synthesis of cyclic peptides Dichotomin, and synthetic proteins including ubiquitin, ?-synuclein and histone H2A.

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