Synthesis of N-methylated cyclic peptides
Synthesis of N-methylated cyclic peptides
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DOI：
10.1038/nprot.2011.450
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发表时间：
2012-03-01
期刊：
影响因子：
14.8
通讯作者：
Kessler, Horst
中科院分区：
文献类型：
--
作者：
Chatterjee, Jayanta;Laufer, Burkhardt;Kessler, Horst
该方案提出了n -甲基化环肽合成的详细描述。n -甲基化是一种强大的技术，通过在肽酰胺键中引入一个或多个甲基来调节肽的物理化学性质。与肽环化一起，这一过程赋予肽前所未有的药代动力学特性，包括代谢稳定性、膜渗透性甚至口服生物利用度。在这里，我们描述了两种简化的线性肽在固体载体上的n -甲基化方法，可以在不到2小时内完成，适用于任何氨基酸。最后，我们还描述了两种肽环化方法，它们可以用来获得n -甲基化的环肽，并且不限于特定的肽序列。使用这种方法，可以在4-5天内合成多个n -甲基化环肽。
This protocol presents a detailed description of the synthesis of N-methylated cyclic peptides. N-methylation is a powerful technique to modulate the physicochemical properties of peptides by introducing one or more methyl groups into the peptidic amide bonds. Together with peptide cyclization, this procedure confers unprecedented pharmacokinetic properties to the peptides, including metabolic stability, membrane permeability and even oral bioavailability. Here we describe two simplified methods of N-methylation of linear peptides on solid supports, which can be performed in less than 2 h and are applicable to any amino acid. Finally, we also describe two methods of peptide cyclization, which can be used to obtain the N-methylated cyclic peptide and which are not limited to specific peptide sequences. With this protocol, multiply N-methylated cyclic peptides can be synthesized in as little as 4-5 d.