Matsumoto Emiko, Fujita Yuko, Okada Yohei, Kauppinen Esko I, Kamiya Hidehiro, Chiba Kazuhiro
Department of Applied Biological Chemistry, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo, 183-8509, Japan.
Department of Chemical Engineering, Tokyo University of Agriculture and Technology, 2-24-16 Naka-cho, Koganei, Tokyo, 184-8588, Japan.
J Pept Sci. 2015 Sep;21(9):691-5. doi: 10.1002/psc.2791. Epub 2015 Jul 22.
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.
C末端酰胺化是肽类最常见的修饰之一，且在生物活性肽中经常出现。然而，C末端修饰必须具有创新性，因为目前肽的化学合成技术主要依赖于使用C末端保护载体。因此，必须在去除此类载体后进行，这使得反应后处理和产物分离变得复杂。在此背景下，疏水性苄胺作为载体成功地添加到了可溶性标签辅助液相肽合成的不断扩展的工具库中，从而实现了ABT-510（2）的全合成。尽管本研究中使用的是乙酰胺形成类型，但不同类型的疏水性苄胺也可以通过通用的一步还原胺化反应简单地设计和制备。肽合成最后一步脱保护中使用的标准酸性处理得到了所需的C末端仲酰胺化肽，且没有差向异构化。
