N→S Acyl-Transfer-Mediated Synthesis of Peptide Thioesters Using Anilide Derivatives

Abstract

N-->S acyl-transfer-mediated synthesis of peptide thioesters utilizing an N-aminoacyl-N-sulfanylethylaminobenzoic acid derivative has been examined. The developed synthetic methodology for peptide thioesters is compatible with Fmoc solid-phase peptide synthesis (SPPS).

From protein total synthesis to peptide transamidation and metathesis: playing with the reversibility of N,S-acyl or N,Se-acyl migration reactions

“…One important step toward the design of mild transamidation and amide metathesis reactions that operate with peptide substrates in water was inspired by recent advances in the design of N,S-acyl shift systems ( Figure 3) [13][14][15][16][17][18][19][20]21 ]. Indeed, some N-(2-sulfanylethyl) amides are able to rearrange into transient thioesters by spontaneous acyl migration from nitrogen to sulfur.…”

“…Indeed, some N-(2-sulfanylethyl) amides are able to rearrange into transient thioesters by spontaneous acyl migration from nitrogen to sulfur. Subsequent in situ exchange with an exogenous thiol may then be performed to produce more stable peptide thioesters which can be isolated [14,15,17,19,20,22]. …”

Progress in Chemical Synthesis of Peptides and Proteins

“…Other systems that utilize N ? S acyl transfer to produce thioesters are reviewed below [66][67][68][69][70][71].…”

“…Tsuda reported N ? S acyl transfer-mediated synthesis of peptide thioesters using anilide derivatives [71].…”

Application of N–C- or C–N-directed sequential native chemical ligation to the preparation of CXCL14 analogs and their biological evaluation

“…This linker system allows facile synthesis of peptide thioesters by N-S acyl transfer. 28 Standard Fmoc SPPS on resin 8 followed by deprotection with a TFA-based reagent cocktail gave deprotected peptide anilide resin 10. Subsequent treatment of 10 with 4 M HCl/DMF in the presence of 1% (w/v) tris(2-carboxyethyl)phosphine hydrochloride (TCEP) gave peptide thioester resin 11 via N-S acyl transfer on the resin.…”