University of Copenhagen, Faculty of Life Sciences, IGM, Section for Nanobioscience, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.
Chem Soc Rev. 2012 Mar 7;41(5):1826-44. doi: 10.1039/c1cs15214a. Epub 2011 Oct 20.
The highly refined organic chemistry in solid-phase synthesis has made it the method of choice not only to assemble peptides but also small proteins - mainly on a laboratory scale but increasingly also on an industrial scale. While conductive heating occasionally has been applied to peptide synthesis, precise microwave irradiation to heat the reaction mixture during coupling and N(α)-deprotection has become increasingly popular. It has often provided dramatic reductions in synthesis times, accompanied by an increase in the crude peptide purity. Microwave heating has been proven especially relevant for sequences which might form β-sheet type structures and for sterically difficult couplings. The beneficial effect of microwave heating appears so far to be due to the precise nature of this type of heating, rather than a peptide-specific microwave effect. However, microwave heating as such is not a panacea for all difficulties in peptide syntheses and the conditions may need to be adjusted for the incorporation of Cys, His and Asp in peptides, and for the synthesis of, for example, phosphopeptides, glycopeptides, and N-methylated peptides. Here we provide a comprehensive overview of the advances in microwave heating for peptide synthesis, with a focus on systematic studies and general protocols, as well as important applications. The assembly of β-peptides, peptoids and pseudopeptides are also evaluated in this critical review (254 references).
固相合成中高度精制的有机化学使得它不仅成为组装肽的首选方法，也成为了合成小蛋白质的首选方法——主要是在实验室规模上，但也越来越多地在工业规模上。虽然导电加热偶尔应用于肽合成，但在偶联和 N（α）脱保护过程中精确的微波辐射来加热反应混合物已变得越来越流行。它通常可以显著缩短合成时间，并提高粗肽的纯度。微波加热已被证明对可能形成β-折叠类型结构的序列和空间位阻困难的偶联特别有效。到目前为止，微波加热的有益效果似乎归因于这种加热方式的精确性质，而不是肽的特定微波效应。然而，微波加热本身并不是解决肽合成中所有困难的万能药，可能需要根据情况调整条件，以适应 Cys、His 和 Asp 掺入肽中，以及合成磷酸肽、糖肽和 N-甲基化肽的需要。在这里，我们全面概述了微波加热在肽合成中的进展，重点介绍了系统研究和一般方案，以及重要的应用。在这篇评论中，还评估了β-肽、肽类和假肽的组装（254 篇参考文献）。
