title: Extending synthetic access to proteins with a removable acyl transfer auxiliary.
abstract: A chemo- and regioselective auxiliary-mediated peptide ligation has been developed that is effective under nonidealized conditions for the synthesis of proteins. This general amide bond ligation utilizes a removable auxiliary that is analogous to the role of cysteine in native chemical ligation, combining chemoselective thioester exchange with efficient regioselective intramolecular acyl transfer. Acid lability and improved ligation efficiency were introduced into the 2-mercaptobenzyl auxiliary by increasing the electron density of the aromatic ring. The 62 amino acid SH3 domain from alpha-spectrin was synthesized using the auxiliary-mediated ligation at a Lys-Gly sequence. The auxiliary was removed with TFA and scavengers from the ligated product. This methodology enables unprotected peptides to be coupled at noncysteine ligation sites expanding the scope of protein synthesis and semisynthesis.
authors.affiliation: Department of Cell Biology, The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: John
authors.initials: J
authors.lastname: Offer
authors.forename: C N C
authors.initials: CN
authors.lastname: Boddy
authors.forename: Philip E
authors.initials: PE
authors.lastname: Dawson
mesh_terms: D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D003545:Cysteine / Q000737:chemistry; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011506:Proteins / Q000138:chemical synthesis*; D018909:src Homology Domains
chemical_list: D010455:Peptides; D011506:Proteins; D003545:Cysteine