Orthogonal Deprotection of Cys Protecting Groups using Palladium(II) Complexes for the Synthesis of Modified Peptides and Proteins
Herein we report for the first time on our findings about orthogonal activities of Pd(II) complexes in the synthesis of modified peptides and proteins. In addition to our previously reported uses of Pd(II) complexes in the removal of various Cys protecting groups in highly efficient manner,1-4 we found that Pd(II) can unmask Cys(t-butyl) in peptides under aqueous conditions. With this in hand, we developed new conditions, which enable orthogonal removal of highly useful Cys protecting groups, including thiazolidine (Thz), acetamidomethyl (Acm) and t-butyl, assisted by Pd(II). We succeeded to remove the Thz with (AllylPdCl)2 in aqueous buffer without affecting the Acm protecting group in the presence of glutathione (GSH) in equal molar ratio to the Pd(II). However, with higher amounts of Pd(II) relative to GSH, the Acm deprotection proceeded smoothly. Under these conditions t-butyl protecting group is stable and only using unique conditions with Pd(II) we observed efficient removal of the t-butyl. These novel findings enabled us to explore the preparation of a library of peptides bearing different modifications by selective deprotection and alkylation steps. Together, this opens new opportunities in peptide and protein chemistry and chemical biology, which we are currently exploring.
References:
1. Jbara, S. K. Maity, M .Seenaiah, A. Brik, J. Am. Chem. Soc. 2016, 138, 5069–5075.
2. K. Maity, M. Jbara, S. Laps, A. Brik, Angew. Chem. Int. Ed. 2016, 55,8108–8112.
3. K. Maity, G. Mann, M. Jbara, S. Laps, G. Kamnesky, A. Brik, Org. Lett. 2016, 18,3026–3029.
4. Jbara, S. Laps, S. K. Maity, A. Brik, Chem. Eur .J. 2016, 22,14851–14855.
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