Fukue Fukao

Click Peptide concept: o-acyl isopeptide of islet amyloid polypeptide as a nonaggregative precursor molecule.

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 IAPPs intense and uncontrollable self‐assembling nature.