Oral Presentation 5th Modern Solid Phase Peptide Synthesis Symposium 2015

N-Sulfanyethylanilide peptide as a crypto thioester for protein chemical synthesis (#18)

Akira Otaka 1
  1. Institute of Biomedical Sciences and Graduate School of Pharmaceutical Sciences, Tokushima University, Tokushima, Japan

Native chemical ligation (NCL), which features the use of peptide thioesters, is as among the most useful ligation reactions in chemical protein synthesis. Requisite thioesters have conventionally been synthesized using Boc SPPS; however, the increasing use of Fmoc SPPS requires an efficient preparative protocol for thioesters that is fully compatible with Fmoc chemistry. N-Sulfanylethylanilide (SEAlide) peptide was initially developed as a thioester precursor suitable for Fmoc SPPS.1 Preliminary study on the SEAlide peptide indicated that the amide-type SEAlide could be converted to the corresponding thioester-type SEAlide only under acidic conditions via N–S acyl transfer reaction; however, continuing detailed investigation disclosed that the amide-type unit can be directly involved in NCL in the presence of phosphate salts even under neutral conditions without pre-conversion to the corresponding thioester.2 That is, participation of the SEAlide peptide in NCL can be tuned by the presence or absence of phosphate salts in the reaction mixture. This interesting feature of the SEAlide peptide enables an N–to–C-directive one-pot/sequential NCL for protein chemical synthesis.3-5 In this presentation, application of the SEAlide peptides to an efficient synthesis of GM2AP proteins consisting of 162-residue is presented. Additionally, several new findings on the SEAlide unit will be discussed.

  1. N-S Acyl-transfer-mediated synthesis of peptide thioesters using anilide derivatives. S. Tsuda, A. Shigenaga, K. Bando, and A. Otaka. Org. Lett. 2009, 11, 823-826.
  2. N-Sulfanylethylanilide peptide as a crypto-thioester peptide K. Sato, A. Shigenaga, K. Tsuji, S. Tsuda, Y. Sumikawa, K. Sakamoto, and A. Otaka. ChemBioChem 2011, 12, 1840-1844.
  3. One-pot/sequential native chemical ligation using N-sulfanylethylanilide peptide. A. Otaka, K. Sato, H. Ding, and A. Shigenaga. Chem. Record, 2012, 12, 479-490.
  4. Chemical Synthesis of Biologically Active Monoglycosylated GM2-activator Protein Analog Using N-Sulfanylethylanilide Peptide. K. Sato, A. Shigenaga, K. Kitakaze, K. Sakamoto, D. Tsuji, K. Itoh, and A. Otaka. Angew. Chem. Int. Ed. 2013, 52, 7855-7859.
  5. Chemical synthesis of proteins using N-sulfanylethylanilide peptides, based on N-S acyl transfer chemistry. A. Otaka, K. Sato, and A. Shigenaga. Topics Current Chem. 2015, 363, 33-56.