title: Biomimetic Synthesis of Insulin Enabled by Oxime Ligation and Traceless "C-Peptide" Chemical Excision.
abstract: For decades, insulin has represented a preeminent synthetic target. Recently introduced "biomimetic" strategies based on convertible single-chain precursors require incorporation of a chemical linker or a unique proteolytic site, which limits their practicality. In this approach the A- and B-chains are linked by two sequential oxime ligations followed by disulfide bond formation under redox conditions and linker excision by diketopiperazine (DKP) formation and ester hydrolysis, yielding native two-chain insulin. The method is expected to be applicable to any member of the insulin superfamily.
authors.affiliation: Department of Chemistry, Indiana University , Bloomington, Indiana 47405, United States.
authors.forename: Kishore
authors.initials: K
authors.lastname: Thalluri
authors.affiliation: Novo Nordisk Research Center Indianapolis , 5225 Exploration Drive, Indianapolis, Indiana 46241, United States.
authors.forename: Binbin
authors.initials: B
authors.lastname: Kou
authors.affiliation: Novo Nordisk Research Center Indianapolis , 5225 Exploration Drive, Indianapolis, Indiana 46241, United States.
authors.forename: Vasily
authors.initials: V
authors.lastname: Gelfanov
authors.affiliation: Novo Nordisk Research Center Indianapolis , 5225 Exploration Drive, Indianapolis, Indiana 46241, United States.
authors.forename: John P
authors.initials: JP
authors.lastname: Mayer
authors.affiliation: Novo Nordisk Research Center Indianapolis , 5225 Exploration Drive, Indianapolis, Indiana 46241, United States.
authors.forename: Fa
authors.identifier: 0000-0002-2909-9185
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Chemistry, Indiana University , Bloomington, Indiana 47405, United States.
authors.forename: Richard D
authors.initials: RD
authors.lastname: DiMarchi
mesh_terms: D000595:Amino Acid Sequence; D032701:Biomimetics; D002096:C-Peptide; D007328:Insulin / Q000138:chemical synthesis*; D015394:Molecular Structure; D010091:Oximes
chemical_list: D002096:C-Peptide; D007328:Insulin; D010091:Oximes