Peptide Research Centre, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501, Japan.
Org Biomol Chem. 2022 Nov 16;20(44):8685-8692. doi: 10.1039/d2ob01795d.
Two new recyclable silicon-based hydrophobic tags were developed for installing them at the C-terminal of peptides to increase the solubility in organic solvents and the reactivity of the peptides during liquid-phase peptide synthesis (LPPS). They comprise a siloxy group containing tag and an arylsilyl group containing tag. The hydrophobicity of these tags is much greater than those of previously reported examples. The siloxy group containing tag is compatible with Fmoc-deprotection conditions (Fmoc-chemistry) and hydrogenation conditions (Cbz-chemistry), while the arylsilyl group containing one is resistant to Fmoc-deprotection conditions (Fmoc-chemistry) and Boc-deprotection conditions (Boc-chemistry). Using the siloxy group containing tag, protected DRGN-1, a peptide containing 14 amino acid residues was prepared successfully by using linear synthesis combined with one convergent synthesis step. Using the arylsilyl group containing tag, a poly alanine chain containing 7 alanine residues was synthesized. The arylsilyl group containing tag can also be installed at the N-terminal to elongate the peptides from the N-terminal to the C-terminal. The yields and the solubility of the products in organic solvents in each step were good to excellent with the assistance of these silicon-based tags.
开发了两种新型可回收硅基疏水性标签，用于将其安装在肽的 C 末端，以增加肽在有机溶剂中的溶解度和在液相肽合成（LPPS）过程中的反应性。它们包含一个含硅氧基的标签和一个含芳基硅基的标签。这些标签的疏水性比以前报道的例子大得多。含硅氧基的标签与 Fmoc 脱保护条件（Fmoc 化学）和氢化条件（Cbz 化学）兼容，而含芳基硅基的标签则耐 Fmoc 脱保护条件（Fmoc 化学）和 Boc 脱保护条件（Boc 化学）。使用含硅氧基的标签，通过线性合成与一个收敛合成步骤相结合，成功制备了含有 14 个氨基酸残基的保护 DRGN-1 肽。使用含芳基硅基的标签，合成了含有 7 个丙氨酸残基的聚丙氨酸链。含芳基硅基的标签也可以安装在 N 末端，从而从 N 末端到 C 末端延长肽。在这些硅基标签的辅助下，每个步骤的产物的产率和在有机溶剂中的溶解度都很好到优秀。
