title: Iterative Reducible Ligation to form Homogeneous Penicillamine Cross-linked Polypeptides.
abstract: The syntheses of homogeneous penicillamine disulfide cross-linked polypeptides are reported. Dodecapeptides containing N-terminal, C-terminal, or N- and C-terminal Pen were serially ligated into 36 amino acid polypeptides linked through Cys-Pen, Pen-Cys or Pen-Pen disulfide bonds. Critical to the syntheses was the incorporation of thiazolidine masked Cys and Pen as the N-terminal residues and selective hydrolysis with silver trifluoromethanesulfonate in acidic aqueous conditions to generate a free thiol for subsequent ligation. This approach allows the synthesis of homogeneous disulfide cross-linked polypeptides that have different reductive stabilities and have application in gene delivery by undergoing a tempered reductive triggered release of DNA.
authors.affiliation: Division of Medicinal & Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City IA 52242.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Ericson
authors.affiliation: Division of Medicinal & Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City IA 52242.
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Rice
keywords: Reducible polypeptides; gene delivery; penicillamine; thiazolidine