N-Methylation of Peptides and Proteins: An Important Element for Modulating Biological Functions
N-Methylation of Peptides and Proteins: An Important Element for Modulating Biological Functions
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DOI：
10.1002/anie.201205674
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发表时间：
2013-01-01
影响因子：
16.6
通讯作者：
Kessler, Horst
中科院分区：
文献类型：
--
作者：
Chatterjee, Jayanta;Rechenmacher, Florian;Kessler, Horst
N-甲基化是最简单的化学修饰之一，常发生在原核生物和高等真核生物的多肽和蛋白质中。经过多年的进化，自然界采用了多肽的N-甲基化作为一种巧妙的技术来调节生物功能，通常是作为一种通过生产抗生素来生存的方式。这种微小的结构变化不仅可以动员大的蛋白质复合体(如组蛋白甲基化)，还可以通过选择性识别蛋白质-蛋白质相互作用表面来抑制酶的作用。近年来，通过合成方法的进步，N-甲基化不仅在调节多肽的生物活性和选择性以及药代动力学性质方面，而且在提供新的药物方面，已经开始显示出潜力。在此，我们总结了目前关于N-甲基化在调节多肽的生物、结构和药代动力学特性方面的多功能性的知识。
N‐Methylation is one of the simplest chemical modifications often occurring in peptides and proteins of prokaryotes and higher eukaryotes. Over years of evolution, nature has employedN‐methylation of peptides as an ingenious technique to modulate biological function, often as a mode of survival through the production of antibiotics. This small structural change can not only mobilize large protein complexes (as in the histone methylation), but also inhibits the action of enzymes by selective recognition of protein–protein interaction surfaces. In recent years through the advancement in synthetic approaches, the potential ofN‐methylation has begun to be revealed, not only in modulating biological activity and selectivity as well as pharmacokinetic properties of peptides, but also in delivering novel drugs. Herein, we summarize the current knowledge of the versatility ofN‐methylation in modulating biological, structural, and pharmacokinetic properties of peptides.