title: Click Peptide concept: o-acyl isopeptide of islet amyloid polypeptide as a nonaggregative precursor molecule.
abstract: The O-acyl isopeptide (1) of islet amyloid polypeptide (IAPP), which contains an ester moiety at both Ala8-Thr9 and Ser19-Ser20, was prepared by sequential segment condensation based on the O-acyl isopeptide method. Isopeptide 1 possessed nonaggregative properties, retaining its random coil structure under the acidic conditions; this suggests that the insertion of the O-acyl isopeptide structures in IAPP suppressed aggregation of the molecule. As a result of the rapid O-to-N acyl shift of 1 under neutral pH, in situ-formed IAPP adopted a random-coil structure at the start of the experiment, and then underwent conformational change to α-helix/β-sheet mixed structures as well as aggregation. The click peptide strategy with the nonaggregative precursor molecule 1 could be a useful experimental tool to identify the functions of IAPP, by overcoming the handling difficulties that arise from IAPP's intense and uncontrollable self-assembling nature.
authors.affiliation: Kyoto Pharmaceutical University, Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Yamashina-ku, Kyoto, Japan.
authors.forename: Taku
authors.initials: T
authors.lastname: Yoshiya
authors.forename: Ayano
authors.initials: A
authors.lastname: Higa
authors.forename: Naoko
authors.initials: N
authors.lastname: Abe
authors.forename: Fukue
authors.initials: F
authors.lastname: Fukao
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kuruma
authors.forename: Yuki
authors.initials: Y
authors.lastname: Toda
authors.forename: Youhei
authors.initials: Y
authors.lastname: Sohma
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiso
mesh_terms: D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D057930:Click Chemistry; D058228:Islet Amyloid Polypeptide / Q000737:chemistry; D055666:Lipopeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011498:Protein Precursors
chemical_list: D016564:Amyloid beta-Protein Precursor; D058228:Islet Amyloid Polypeptide; D055666:Lipopeptides; D011498:Protein Precursors