title: Enzyme-catalyzed macrocyclization of long unprotected peptides.
abstract: A glutathione S-transferase (GST) catalyzed macrocyclization reaction for peptides up to 40 amino acids in length is reported. GST catalyzes the selective S(N)Ar reaction between an N-terminal glutathione (GSH, γ-Glu-Cys-Gly) tag and a C-terminal perfluoroaryl-modified cysteine on the same polypeptide chain. Cyclic peptides ranging from 9 to 24 residues were quantitatively produced within 2 h in aqueous pH = 8 buffer at room temperature. The reaction was highly selective for cyclization at the GSH tag, enabling the combination of GST-catalyzed ligation with native chemical ligation to generate a large 40-residue peptide macrocycle.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology , 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Dai
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Spokoyny
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Pentelute
mesh_terms: D002384:Catalysis; D003500:Cyclization; D005978:Glutathione / Q000737:chemistry*; D005982:Glutathione Transferase / Q000378:metabolism*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D010455:Peptides; D010456:Peptides, Cyclic; D005982:Glutathione Transferase; D005978:Glutathione