Wróblewska Aneta, Bak-Sypien Irena I, Paluch Piotr, Wielgus Ewelina, Zając Justyna, Jeziorna Agata, Kaźmierski Sławomir, Potrzebowski Marek J
Division of Structural Studies, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363, Łódź, Poland.
Chemistry. 2024 Aug 6;30(44):e202400177. doi: 10.1002/chem.202400177. Epub 2024 May 29.
We report an idea for the synthesis of oligopeptides using a solvent-free ball milling approach. Our concept is inspired by block play, in which it is possible to construct different objects using segments (blocks) of different sizes and lengths. We prove that by having a library of short peptides and employing the ball mill mechanosynthesis (BMMS) method, peptides can be easily coupled to form different oligopeptides with the desired functional and biological properties. Optimizing the BMMS process we found that the best yields we obtained when TBTU and cesium carbonate were used as reagents. The role of CsCO in the coupling mechanism was followed on each stage of synthesis by H, C and Cs NMR employing Magic Angle Spinning (MAS) techniques. It was found that cesium carbonate acts not only as a base but is also responsible for the activation of substrates and intermediates. The unique information about the BMMS mechanism is based on the analysis of 2D NMR data. The power of BMMS is proved by the example of different peptide combinations, 2+2, 3+2, 4+2, 5+2 and 4+4. The tetra-, penta-, hexa-, hepta- and octapeptides obtained under this project were fully characterized by MS and NMR techniques.
我们报道了一种使用无溶剂球磨法合成寡肽的方法。我们的理念受到积木游戏的启发，在积木游戏中，可以使用不同大小和长度的片段（积木）构建不同的物体。我们证明，通过拥有一个短肽库并采用球磨机械合成（BMMS）方法，可以轻松地将肽偶联形成具有所需功能和生物学特性的不同寡肽。通过优化BMMS过程，我们发现当使用TBTU和碳酸铯作为试剂时，获得的产率最高。在合成的每个阶段，通过采用魔角旋转（MAS）技术的氢、碳和铯核磁共振跟踪碳酸铯在偶联机制中的作用。发现碳酸铯不仅作为碱起作用，还负责底物和中间体的活化。关于BMMS机制的独特信息基于二维核磁共振数据分析。通过不同肽组合（2+2、3+2、4+2、5+2和4+4）的例子证明了BMMS的强大功能。在该项目下获得的四肽、五肽、六肽、七肽和八肽通过质谱和核磁共振技术进行了全面表征。
