title: An iodine-free and directed-disulfide-bond-forming route to insulin analogues.
abstract: An iodine-free synthetic route to insulin analogues has been established via a directed disulfide bond formation strategy. This method is completely compatible with oxidation-sensitive residues. The key step is constructing the third disulfide bond via a novel procedure involving phenylacetylaminomethyl group (Phacm), immobilized Penicillin G Acylase, and Ellman's reagent. We expect that this method could be broadly utilized for synthesizing insulin-like and other cysteine-rich peptides, in particular, where oxidation-sensitive residues are present in the sequence.
authors.affiliation: Lilly Research Laboratories, Indianapolis, Indiana 46285, United States.
authors.forename: Fa
authors.initials: F
authors.lastname: Liu
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Liu
authors.forename: Adam R
authors.initials: AR
authors.lastname: Mezo
mesh_terms: D003545:Cysteine / Q000737:chemistry; D004220:Disulfides / Q000737:chemistry; D007202:Indicators and Reagents / Q000737:chemistry; D061385:Insulins / Q000737:chemistry*; D007455:Iodine / Q000737:chemistry*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010399:Penicillin Amidase / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry
chemical_list: D004220:Disulfides; D007202:Indicators and Reagents; D061385:Insulins; D010455:Peptides; D007455:Iodine; D010399:Penicillin Amidase; D003545:Cysteine