Optimized selective N-methylation of peptides on solid support
Optimized selective N-methylation of peptides on solid support
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DOI：
10.1002/psc.711
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发表时间：
2006-03-01
影响因子：
2.1
通讯作者：
Kessler, H
中科院分区：
文献类型：
--
作者：
Biron, E;Chatterjee, J;Kessler, H
含有N-α-甲基氨基酸的肽表现出令人感兴趣的治疗特性，并且越来越多地被认为是潜在有用的治疗剂。不幸的是，它们的合成受到许多N-α-甲基氨基酸的高价格和不可用性的阻碍。描述了一种高效实用的固体支持物上肽选择性N-甲基化的三步程序。该方法基于众所周知的N-α-芳基磺酰基肽的固相N-甲基化，通过使用硫酸二甲酯和较便宜的DBU作为碱来改进。每一步的程序，胺活化邻-硝基苯磺酰基，选择性N-甲基化和去除磺酰胺基团，在时间和经济方面进行了优化。所述优化的三步程序在35分钟内进行，无溶剂。变化，而不是3小时。用优化的方法制备了含有N-甲基化的常见氨基酸的三肽（Fmoc-Pbe-MeXaa-Leu-OH），以证明其与这些氨基酸的相容性。所述方法允许使用Fmoc固相肽合成在非常短的时间内有效合成含有N-α-甲基氨基酸的肽。版权所有. (c)2005年欧洲肽协会和约翰威利父子公司。
Peptides containing N-alpha-methylamino acids exhibit interesting therapeutic profiles and are increasingly recognized as potentially useful therapeutics. Unfortunately, their synthesis is hampered by the high price and nonavailability of many N-alpha-methylamino acids. An efficient and practical three-step procedure for selective N-methylation of peptides on solid support is described. The procedure was based on the well known solid-phase N-methylation of N-alpha-arylsulfonyl peptides, which was improved by using dimethylsulfate and the less expensive DBU as base. Every step of the procedure, amine activation by an o-nitrobenzenesulfonyl group, selective N-methylation and removal of the sulfonamide group, was optimized in respect of time and economy. The described optimized three-step procedure is performed in 35 min without solvent. changes, instead of 3 h. Tripeptides (Fmoc-Pbe-MeXaa-Leu-OH) containing N-methylated common amino acids were also prepared using the optimized procedure to demonstrate its compatibility with these amino acids. The described procedure allows an efficient synthesis of N-alpha-methylamino acid containing peptides in a very short: time using Fmoc solid-phase peptide synthesis. Copyright. (c) 2005 European Peptide Society and John Wiley & Sons, Ltd.