"Click Peptide" Concept: O-Acyl Isopeptide of Islet Amyloid Poly- peptide As a non-aggregative precursor molecule.
"Click Peptide" Concept: O-Acyl Isopeptide of Islet Amyloid Poly- peptide As a non-aggregative precursor molecule.
复制标题
“点击肽”概念：胰岛淀粉样多肽的O-酰基异肽 作为非聚集性前体分子。
DOI：
10.1002/cbic.201100025
复制
发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Yoshiaki Kiso
中科院分区：
文献类型：
--
作者：
Taku Yoshiya;Ayano Higa;Naoko Abe;Fukue Fukao;Tomomi Kuruma;Youhei Sohma;Yoshiaki Kiso
胰岛淀粉样多肽(IAPP)的O-酰基异肽(1)在Ala8-Thr9和Ser19-Ser20处均含有酯部分，是基于O-酰基异肽方法通过顺序片段缩合制备的。异肽1具有非聚集性，在酸性条件下仍保持其无规卷曲结构；这表明 IAPP 中 O-酰基异肽结构的插入抑制了分子的聚集。由于1在中性pH下快速O-N酰基转移，原位形成的IAPP在实验开始时采用随机螺旋结构，然后经历构象变化为α-螺旋/β-折叠混合结构以及聚集。通过克服因 IAPP 强烈且不可控的自组装性质而产生的处理困难，使用非聚集前体分子的点击肽策略可能成为鉴定 IAPP 功能的有用实验工具。
TheO‐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 theO‐acyl isopeptide method. Isopeptide1possessed nonaggregative properties, retaining its random coil structure under the acidic conditions; this suggests that the insertion of theO‐acyl isopeptide structures in IAPP suppressed aggregation of the molecule. As a result of the rapid O‐to‐N acyl shift of1under 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 molecule1could 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.