title: Synthesis of the bis-cystinyl-fragment 225-232/225'-232' of the human IgGl hinge region.
abstract: In human IgGl the two heavy chains are crosslinked in the central portion of the molecule by two disulfide bridges forming a double chain bis-cystinyl cyclic peptide in parallel alignment. For our synthetic studies we have chosen the sequence portion 225-232/225'-232', i.e. [H-Thr-C1ys-Pro-Pro-C1ys-Pro-Ala-Pro-OH]2. By the use of a combination of the S-tert.-butylthio and the S-acetamidomethyl groups selective cysteine pairings in two successive steps produced the hinge hexadecapeptide in parallel and antiparallel alignment as homogeneous and well characterized compounds. Thiol disulfide interchange experiments on the antiparallel dimer led to over 90% conversion to the parallel isomer. Similarly random air-oxidation was found to generate again mainly the parallel dimer, thus strongly suggesting that this sequence portion contains sufficient structural information for a correct assembly of the two heavy chains of immunoglobulins without decisive contribution of a protein disulfide isomerase.
authors.affiliation: Department of Peptide Chemistry, Max Planck Institute for Biochemistry, Martinsried, FRG.
authors.forename: E
authors.initials: E
authors.lastname: Wünsch
authors.forename: L
authors.initials: L
authors.lastname: Moroder
authors.forename: S
authors.initials: S
authors.lastname: Göhring-Romani
authors.forename: H J
authors.initials: HJ
authors.lastname: Musiol
authors.forename: W
authors.initials: W
authors.lastname: Göhring
authors.forename: G
authors.initials: G
authors.lastname: Bovermann
mesh_terms: D000595:Amino Acid Sequence; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003545:Cysteine; D003553:Cystine; D004220:Disulfides; D006801:Humans; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D046911:Macromolecular Substances; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000138:chemical synthesis*; D013438:Sulfhydryl Compounds
chemical_list: D004220:Disulfides; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D046911:Macromolecular Substances; D009842:Oligopeptides; D010446:Peptide Fragments; D013438:Sulfhydryl Compounds; D003553:Cystine; D003545:Cysteine