SEAlide as thioester equivalent for chemical synthesis of proteins — ASN Events
  1. Schedule
  2. Session 5 SP Protein Synthesis
  3. SEAlide as thioester equivalent for chemical synthesis of proteins

SEAlide as thioester equivalent for chemical synthesis of proteins (#20)

Akira Shigenaga 1
  1. The University of Tokushima, Tokushima, Japan

Native chemical ligation (NCL) is one of the most useful methods for the chemical synthesis of proteins.1 Peptide thioesters are required for the NCL to chemoselectively acylate N-terminal cysteinyl peptides to afford ligated peptides and proteins. However, preparation of peptide thioesters using Fmoc-based solid-phase peptide synthesis (Fmoc SPPS) that is widely used to prepare peptides is complicated because thioesters decompose under Fmoc-removal conditions with piperidine. Therefore, practical methodology for preparation of peptide thioesters, compatible to Fmoc SPPS, is highly demanded.


In this context, we developed an N-sulfanylethylaniline linker that enables construction of peptides as an amide type N-acylated N-sulfanylethylanilide (SEAlide) by Fmoc SPPS followed by conversion of the amide to the thioester by N-S acyl transfer in 4 M HCl/DMF to yield the peptide thioesters.2 Furthermore, it was unexpectedly found that the SEAlide could work as a thioester in a neutral phosphate buffer but not in a HEPPS buffer.3 In this presentation, chemistry of the SEAlide including one-pot multi-fragment ligation to prepare proteins will be reported.4

  1. P. E. Dawson, T. W. Muir, I. Clark-Lewis, S. B. H. Kent, Science 1994, 266, 776-779; S. B. H. Kent, Chem. Soc. Rev. 2009, 38, 338-351.
  2. S. Tsuda, A. Shigenaga, K. Bando, A. Otaka, Org. Lett. 2009, 11, 823-826; A. Otaka, K. Sato, H. Ding, A. Shigenaga, Chem. Record 2012, 12, 479-490, and references therein.
  3. K. Sato, A. Shigenaga, K. Tsuji, S. Tsuda, Y. Sumikawa, K. Sakamoto, A. Otaka, ChemBioChem 2011, 12, 1840-1844.
  4. K. Sato, A. Shigenaga, K. Kitakaze, K. Sakamoto, D. Tsuji, K. Itoh, A. Otaka, Angew. Chem. Int. Ed. 2013, 52, 7855-7859.