Synthesis of an O-acyl isopeptide by using native chemical ligation in an aqueous solvent system.
Synthesis of an O-acyl isopeptide by using native chemical ligation in an aqueous solvent system.
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在水性溶剂系统中使用天然化学连接合成 O-酰基异肽。
DOI：
10.1002/psc.2622
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发表时间：
2014
影响因子：
2.1
通讯作者：
川島 浩之
中科院分区：
文献类型：
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作者：
Ling Chen;Masashi Okada;et al;川島 浩之
O-酰基异肽，其中羟基氨基酸残基(如丝氨酸和苏氨酸)上的然后-酰基连接被ANO-酰基连接所取代，通常会抑制来自相应母肽的不利的聚集特性。在这里，我们报告了利用天然化学连接方法合成34-聚焦谷氨酸-Adan(2)的ANO-酰基异肽，这是遗传性家族性丹麦痴呆淀粉样沉积的一种成分。焦谷氨酸-Adan(1-21)-SCH_2CH_2SO_3-−Na~+(3)和Cys22-O-酰基异肽(4)在水溶液中的天然化学连接反应顺利，得到了连接的O-酰基异肽(5)。随后二硫键的形成和烯丙氧基羰基的去保护，再经高效液相色谱纯化得到2，总收率合理。2通过O-到-N酰基迁移反应转化为母体多肽1。顺序法，即(1)茶酰基异肽的天然化学连接，(2)以茶酰基异肽形式的高效液相纯化，(3)O-到-N-酰基迁移到所需的多肽中，将有助于解决蛋白质化学合成过程中疏水性多肽的高效液相色谱纯化问题。版权所有©2014欧洲多肽协会和John Wiley&Sons，Ltd.
O‐Acyl isopeptides, in which theN‐acyl linkage on the hydroxyamino acid residue (e.g. Ser and Thr) is replaced by anO‐acyl linkage, generally suppress unfavorable aggregation properties derived from the corresponding parent peptides. Here, we report the synthesis of anO‐acyl isopeptide of 34‐mer pyroGlu‐ADan (2), a component of amyloid deposits in hereditary familial Danish dementia, by using native chemical ligation. Native chemical ligation of pyroGlu1‐ADan(1‐21)‐SCH2CH2SO3−Na+(3) and Cys22‐O‐acyl isopeptide (4), in which the amino group of the Ser29residue at the isopeptide moiety was protected by an allyloxycarbonyl group, proceeded well in an aqueous solvent to yield a ligatedO‐acyl isopeptide (5). Subsequent disulfide bond formation and deprotection of the allyloxycarbonyl group followed by HPLC purification gave 2 with a reasonable overall yield. 2 was converted to the parent peptide 1 via an O‐to‐N acyl migration reaction. The sequential method, namely (i) native chemical ligation of theO‐acyl isopeptide, (ii) HPLC purification as theO‐acyl isopeptide form, and (iii) O‐to‐N acyl migration into the desired polypeptide, would be helpful to solve problems with HPLC purification of hydrophobic polypeptides in the process of chemical protein synthesis. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.