Piperazine and DBU: a safer alternative for rapid and efficient Fmoc deprotection in solid phase peptide synthesis
Piperazine and DBU: a safer alternative for rapid and efficient Fmoc deprotection in solid phase peptide synthesis
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DOI：
10.1039/c5ra23441g
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发表时间：
2015-01-01
期刊：
影响因子：
3.9
通讯作者：
Gupta, Sharad
中科院分区：
文献类型：
--
作者：
Ralhan, Krittika;KrishnaKumar, V. Guru;Gupta, Sharad
在固相肽合成（SPPS）中，经常与靶肽共杂交的缺失序列的污染仍然是主要挑战，因为这些杂质可以显著影响靶肽的性质。在这里，我们报告了一种有效的Fmoc脱保护溶液，含有哌嗪和DBU，可以在不到一分钟的时间内完全去除Fmoc基团。动力学研究表明，该组合在快速性方面与哌啶相当。我们证明了哌嗪/DBU解决方案的效率，通过合成的聚丙氨酸延伸与缺失的产品发生由于部分Fmoc脱保护显着减少。我们通过成功合成四个易于聚集的困难肽序列来验证脱保护溶液的效用。我们进一步证明，这种组合也可以用于合成天冬酰亚胺和差向异构化倾向的序列时，补充1%的甲酸和2-氯三苯甲基氯树脂是兼容的。我们的结论是，哌嗪/DBU可以作为一个更安全和有效的替代品，在Fmoc-SPPS哌啶。
In Solid Phase Peptide Synthesis (SPPS), contamination with deletion sequences which often co-elute with the target peptide continues to be a major challenge as these impurities can significantly affect the target peptide's properties. Here, we report an efficient Fmoc-deprotection solution containing piperazine and DBU which can cause complete removal of the Fmoc group in less than a minute. This combination rivals piperidine in speediness as revealed by kinetic studies. We demonstrate the efficiency of the piperazine/DBU solution by synthesizing the polyAla stretch with a significant reduction of deletion products occurring due to partial Fmoc deprotection. We verify the utility of the deprotection solution by successfully synthesizing four aggregation prone difficult peptide sequences. We further demonstrate that this combination can also be used to synthesize aspartimide and epimerization prone sequences when supplemented with 1% formic acid and is compatible with 2-chlorotrityl chloride resin. We conclude that piperazine/DBU can be used as a safer and effective alternative to piperidine in Fmoc-SPPS.