Hydrophobic benzyl amines as supports for liquid-phase C-terminal amidated peptide synthesis: application to the preparation of ABT-510
Hydrophobic benzyl amines as supports for liquid-phase C-terminal amidated peptide synthesis: application to the preparation of ABT-510
复制标题
疏水性苄胺作为液相C端酰胺化肽合成的载体：在ABT-510制备中的应用
DOI：
10.1002/psc.2791
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Kazuhiro Chiba
中科院分区：
文献类型：
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作者：
Emiko Matsumoto;Yuko Fujita;Yohei Okada;Esko I. Kauppinen;Hidehiro Kamiya;Kazuhiro Chiba
C末端酰胺化是肽的最常见修饰之一，并且经常在生物活性肽中发现。然而，C末端修饰必须是创造性的，因为目前肽的化学合成技术主要是使用C末端保护支持物。因此，必须在拆除此类支撑物后进行，使反应后处理和产物分离变得复杂。在这种情况下，疏水性苄胺被成功地添加到可溶性标签辅助液相肽合成的不断增长的工具箱中作为支持物，从而实现了ABT-510的全合成（2）。虽然在本工作中使用了乙基酰胺形成类型，但也可以通过一步中的多功能还原胺化来简单地设计和制备不同类型的疏水性苄基胺。在肽合成的最终脱保护步骤中使用的标准酸处理得到所需的C末端二级酰胺化肽，没有差向异构化。版权所有© 2015欧洲肽协会和约翰威利父子有限公司。
C‐terminal amidation is one of the most common modification of peptides and frequently found in bioactive peptides. However, the C‐terminal modification must be creative, because current chemical synthetic techniques of peptides are dominated by the use of C‐terminal protecting supports. Therefore, it must be carried out after the removal of such supports, complicating reaction work‐up and product isolation. In this context, hydrophobic benzyl amines were successfully added to the growing toolbox of soluble tag‐assisted liquid‐phase peptide synthesis as supports, leading to the total synthesis of ABT‐510 (2). Although an ethyl amide‐forming type was used in the present work, different types of hydrophobic benzyl amines could also be simply designed and prepared through versatile reductive aminations in one step. The standard acidic treatment used in the final deprotection step for peptide synthesis gave the desired C‐terminal secondary amidated peptide with no epimerization. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.