Molecular Biophysics Unit, Indian Institute of Science, Bangalore, 560012, India.
J Pept Sci. 2020 Apr;26(4-5):e3248. doi: 10.1002/psc.3248. Epub 2020 Mar 22.
The unique physicochemical properties of a thioamide bond, which is an ideal isostere of an amide bond, have not been fully exploited because of the tedious synthesis of thionated amino acid building blocks. Here, we report a purification-free and highly efficient synthesis of thiobenzotriazolides of Fmoc-protected and orthogonally protected 20 naturally occurring amino acids including asparagine, glutamine, and histidine. The near-quantitative conversion to the respective thioamidated peptides on solid support demonstrates the robustness of the synthetic route. Furthermore, the unaltered incorporation efficiency of thiobenzotriazolides from their stock solution till 48 h suggests their compatibility toward automated peptide synthesis. Finally, utilizing an optimized cocktail of 2% DBU + 5% piperazine for fast Fmoc-deprotection, we report the synthesis of a thioamidated Pin1 WW domain and thioamidated GB1 directly on solid support.
硫酰胺键具有独特的物理化学性质，是酰胺键的理想等排体，但由于硫代氨基酸砌块的合成过程繁琐，其尚未得到充分利用。在这里，我们报告了一种无需纯化且高效的合成方法，可用于制备 Fmoc 保护和正交保护的 20 种天然存在的氨基酸（包括天冬酰胺、谷氨酰胺和组氨酸）的硫代苯并三唑化物。在固体载体上，这些硫代苯并三唑化物几乎定量转化为相应的硫酰胺化肽，证明了该合成路线的稳健性。此外，从其储备溶液到 48 小时，硫代苯并三唑化物的掺入效率保持不变，表明其与自动化肽合成相容。最后，利用 2% DBU + 5%哌嗪的优化混合物进行快速 Fmoc 脱保护，我们报告了在固体载体上直接合成硫酰胺化 Pin1 WW 结构域和硫酰胺化 GB1。
