Reduction of cysteine-S-protecting groups by triisopropylsilane.
Reduction of cysteine-S-protecting groups by triisopropylsilane.
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DOI：
10.1002/psc.3130
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发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Hondal RJ
中科院分区：
文献类型：
--
作者：
Ste Marie EJ;Hondal RJ
三异丙基硅烷(TIS)是一种受阻的氢硅烷，长期以来一直被用作阳离子清除剂，用于多肽合成过程中氨基酸保护基团的去除。然而，它作为还原剂主动清除S保护基团的能力在很大程度上被多肽界误解了。在这里，我们提供了强有力的证据表明，在37℃的三氟乙酸(TFA)存在下，TIS可以作为还原剂促进半胱氨酸(Cys)残基的脱除，促进半胱氨酸(Cys)残基的脱除。在本研究中，Cys保护基团在TFA/TIS(98/2)中的稳定性顺序为：Cys(MOB)>；Cys(ACM)>；Cys(BUT)，Cys(BUT)，特别是Cys(Mob)。出乎意料的是，我们发现TIS除了促进保护基团的去除外，还促进了二硫键的形成。根据我们的结果，TIS可以被视为一种潜在的去保护剂，而不仅仅是去保护鸡尾酒中的清道夫，所以我们的结果增加了将TIS用于多肽合成后Cys保护基的正交脱保护策略的可能性。我们还在这些反应条件下测试了其他常见的清除剂，发现硫代苯甲醚和三乙基硅烷在加强脱除保护和催化二硫化物形成方面与TIS具有类似的效果。我们在这里报告的发现表明，当需要保留半胱氨酸保护基团时，应该仔细考虑所使用的清除剂的类型。此外，还应考虑清除剂的浓度、反应温度和反应时间。三异丙基硅烷可以作为去保护剂从半胱氨酸中去除S保护基团。当在多肽去保护鸡尾酒中使用烷基硅烷清除剂时，在希望将保护基团保持在半胱氨酸上的条件下应谨慎。与烷基硅烷脱保护反应的浓度、温度和时间长度都是重要的考虑因素。
Triisopropylsilane (TIS), a hindered hydrosilane, has long been utilized as a cation scavenger for the removal of amino acid protecting groups during peptide synthesis. However, its ability to actively remove S-protecting groups by serving as a reductant has largely been mischaracterized by the peptide community. Here, we provide strong evidence that TIS can act as a reducing agent to facilitate the removal of acetamidomethyl (Acm), 4-methoxybenzyl (Mob), and tert-butyl (But) protecting groups from cysteine (Cys) residues in the presence of trifluoroacetic acid (TFA) at 37 °C. The lability of the Cys protecting groups in TFA/TIS (98/2) in this study are in the order: Cys(Mob) > Cys(Acm) > Cys(But), with Cys(Mob) being especially labile. Unexpectedly, we found that TIS promoted disulfide formation in addition to aiding in the removal of the protecting group. Our results raise the possibility of using TIS in orthogonal deprotection strategies of Cys-protecting groups following peptide synthesis as TIS can be viewed as a potential deprotection agent instead of merely a scavenger in deprotection cocktails based on our results. We also tested other common scavengers under these reaction conditions and found that thioanisole and triethylsilane were similarly effective as TIS in enhancing deprotection and catalyzing disulfide formation. Our findings reported herein show that careful consideration should be given to the type of scavenger used when it is desirable to preserve the Cys-protecting group. Additional consideration should be given to the concentration of scavenger, temperature of the reaction, and reaction time. Triisopropylsilane can act as a deprotection reagent to remove S-protecing groups from cysteine. Care should be taken when using alkylsilane scavengers in peptide deprotection cocktails under conditions where it is desired to keep the protecting group on cysteine. The concentration, temperature, and length of time of the deprotection reaction with alkylsilanes are all important factors for consideration.
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影响因子：
2.1
作者：
Harris, Katharine M.;Flemer, Stevenson, Jr.;Hondal, Robert J.
通讯作者：
Hondal, Robert J.
DOI：
10.1039/p19850002065
发表时间：
1985-01-01
期刊：
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1
影响因子：
--
作者：
ATHERTON, E;SHEPPARD, RC;WARD, P
通讯作者：
WARD, P
影响因子：
1.8
作者：
Singh, PR;Rajopadhye, M;Williams, NE
通讯作者：
Williams, NE
影响因子：
2.9
作者：
Muttenthaler, Markus;Ramos, Yesica Garcia;Alewood, Paul F.
通讯作者：
Alewood, Paul F.
影响因子：
1.8
作者：
PEARSON, DA;BLANCHETTE, M;GUINDON, CA
通讯作者：
GUINDON, CA