Highly efficient solid phase synthesis of large polypeptides by iterative ligations of bis(2-sulfanylethyl)amido (SEA) peptide segments

Laurent Raibaut (1) , Hélène Adihou (2) , Rémi Desmet (1) , Agnès F. Delmas (2) , Vincent Aucagne (2) , Oleg Melnyk (1)

1 IBLI - Institut de biologie de Lille - IBL
2 CBM - Centre de biophysique moléculaire

Up to now, the advantages of solid phase protein synthesis have been largely under-utilized due to the difficulty of designing a simple and efficient elongation cycle enabling the concatenation of unprotected peptide segments. The combination of selective N-terminal anchoring (N3-Esoc linker) with the blocked thioester properties of SEAoff group enabled the solid phase concatenation of unprotected peptide segments by N-to-C sequential formation of native peptide bonds. The strategy was applied to the synthesis of a 60 amino acid-long latent peptide thioester or to the assembly of five peptide segments to give a 15 kDa polypeptide.

Mots clés: protein total synthesis; SEA native peptide ligation; bis(2-sulfanylethyl)amido; thioester; solid phase; click chemistry; azide; alkyne

Domaines: Chimie organique

Laurent Raibaut, Hélène Adihou, Rémi Desmet, Agnès F. Delmas, Vincent Aucagne, et al.. Highly efficient solid phase synthesis of large polypeptides by iterative ligations of bis(2-sulfanylethyl)amido (SEA) peptide segments. Chemical Science, 2013, 4, pp.4061-4066. ⟨10.1039/c3sc51824h⟩. ⟨hal-00944814v2⟩