Historically, methods to remove the 4‐methoxybenzyl (Mob)–protecting group from selenocysteine (Sec) in peptides have used harsh and toxic reagents. The use of 2,2′‐dithiobis‐5‐nitropyridine (DTNP) is an improvement over these methods; however, many wash steps are required to remove the by‐product contaminant 5‐nitro‐2‐thiopyridine. Even with many washes, excess DTNP adheres to the peptide. The final product needs excess purification to remove these contaminants. It was recently discovered by our group that hindered hydrosilanes could be used to reduce Cys(Mob). We sought to apply a similar methodology to reduce Sec(Mob), which we expected to be even more labile. Here, we present a gentle and facile method for deprotection of Sec(Mob) using triethylsilane (TES), phenol, and a variety of other scavengers often used in deprotection cocktails. The different cocktails were all incubated at 40 °C for 4 hours. The combination of TFA/TES/thioanisole (96:2:2) appeared to be the most efficient of the cocktails tested, providing complete deprotection and yielded peptide that was mainly in the diselenide form. This cocktail also showed no evidence of side reactions or significant contaminants in the high‐performance liquid chromatography (HPLC) and mass spectral (MS) analyses. We envision that our new method will allow for a simple and gentle “one‐pot” deprotection of Sec(Mob) following solid‐phase peptide synthesis and will minimize the need for extensive purification steps.

中文翻译：

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轻松去除硒代半胱氨酸中的 4-甲氧基苄基保护基。

从历史上看，从肽中的硒代半胱氨酸 (Sec) 中去除 4-甲氧基苄基 (Mob) 保护基团的方法使用了刺激性且有毒的试剂。2,2'-二硫双-5-硝基吡啶 (DTNP) 的使用是对这些方法的改进；然而，需要许多洗涤步骤来去除副产物污染物 5-硝基-2-硫代吡啶。即使经过多次洗涤，过量的 DTNP 仍会粘附在肽上。最终产品需要过度纯化以去除这些污染物。我们课题组最近发现受阻氢硅烷可用于还原Cys(Mob)。我们试图应用类似的方法来减少 Sec(Mob)，我们预计这种方法会更加不稳定。在这里，我们提出了一种温和且简便的方法，使用三乙基硅烷 (TES)、苯酚和脱保护混合物中经常使用的各种其他清除剂对 Sec(Mob) 进行脱保护。不同的鸡尾酒均在 40°C 下孵育 4 小时。TFA/TES/茴香硫醚 (96:2:2) 的组合似乎是所测试的混合物中最有效的，可提供完全脱保护并产生主要为二硒化物形式的肽。在高效液相色谱 (HPLC) 和质谱 (MS) 分析中，该混合物也没有显示出副反应或显着污染物的证据。我们设想，我们的新方法将允许在固相肽合成后对 Sec(Mob) 进行简单而温和的“一锅”脱保护，并将最大限度地减少大量纯化步骤的需要。