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

• Reversible covalent chemistry and peptide dynamic combinatorial libraries.
• Chemoselective reversible amide bond and peptide bond forming reactions.
• Peptide transamidation and metathesis in water.
• Native chemical ligation (NCL) and thioester or selenoester surrogates.
• N,S(Se)-acyl shift and reversibility of peptide bonds to cysteine and selenocysteine.

Amide forming reactions are central to the field of peptide and protein synthesis and are considered to be poorly reversible reactions owing to the high stability of peptide bonds. One amide-forming reaction is native chemical ligation (NCL) which is driven by a sulfur to nitrogen acyl migration process from a transient thioester intermediate. However, recent studies have revealed the reversibility of the S,N-acyl shift reaction or of the related Se,N-acyl shift process using mild aqueous conditions. Such chemical processes have great potential for the chemoselective formation of peptide bonds to cysteine or selenocysteine, and open novel avenues in the field of peptide transamidation and metathesis reactions.

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