Studies on deprotection of cysteine and selenocysteine side-chain protecting groups
Studies on deprotection of cysteine and selenocysteine side-chain protecting groups
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DOI：
10.1002/psc.795
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发表时间：
2007-02-01
影响因子：
2.1
通讯作者：
Hondal, Robert J.
中科院分区：
文献类型：
--
作者：
Harris, Katharine M.;Flemer, Stevenson, Jr.;Hondal, Robert J.
我们在这里提出了一种简单的方法，用于从半胱氨酸和硒代半胱氨酸的侧链上脱保护对甲氧基苄基和乙酰胺基甲基。该方法使用溶解在TFA中的高度亲电的芳族二硫化物2，2 ′-二硫代双（5-硝基吡啶）（DTNP）和2，2 ′-二硫代二吡啶（DTP）来实现这些迄今难以除去的保护基的除去。事实上，这些试剂在TFA中的溶解起到“活化”它们以进行脱保护反应的作用，因为吡啶环的氮原子的质子化使得二硫键更亲电。因此，这些试剂可以加入到任何用于肽合成的标准裂解混合物中。仅需要亚化学计量量的DTNP来引起对甲氧基苄基的完全去除，需要少至0.2当量来实现70%保护基的去除。为了从半胱氨酸中除去对甲氧基苄基，需要2当量的DTNP和加入茴香硫醚以实现除去。在含硫氨基酸的情况下，茴香硫醚是绝对需要的反应，而它不需要为sclenocysteine。结果与茴香硫醚作为催化剂一致。半胱氨酸的乙酰氨基甲基也可以使用DTNP去除，但需要加入> 15当量才有效。DTP作为脱保护试剂不太稳健。我们还表明，这种化学可用于硒代半胱氨酸和半胱氨酸残基之间的同时环化/脱保护反应，由p-甲氧基苄基保护，形成硒硫键，证明未来的高效用的脱保护方法。版权所有（c）2006欧洲肽协会和约翰威利父子有限公司。
We present here a simple method for deprotecting p-methoxybenzyl groups and acetamidomethyl groups from the sidechains of cysteine and selenocysteine. This method uses the highly elecrophilic, aromatic disulfides 2,2'-dithiobis(5-nitropyridine) (DTNP) and 2,2'-dithiodipyridine (DTP) dissolved in TFA to effect removal of these heretofore difficult- to-remove protecting groups. The dissolution of these reagents in TFA, in fact, serves to 'activate' them for the deprotection reaction because protonation of the nitrogen atom of the pyridine ring makes the disulfide bond more electrophilic. Thus, these reagents can be added to any standard cleavage cocktail used in peptide synthesis.The p-methoxybenzyl group of selenocysteine is easily removed by DTNP. Only sub-stoichiometric amounts of DTNP are required to cause full removal of the p-methoxybenzyl group, with as little as 0.2 equivalents necessary to effect 70% removal of the protecting group. In order to remove the p-methoxybenzyl group from cysteine, 2 equivalents of DTNP and the addition of thioanisole was required to effect removal. Thioanisole was absolutely required for the reaction in the case of the sulfur-containing amino acids, while it was not required for sclenocysteine. The results were consistent with thioanisole acting as a catalyst. The acetamidomethyl group of cysteine could also be removed using DTNP, but required the addition of > 15 equivalents to be effective. DTP was less robust as a deprotection reagent. We also demonstrate that this chemistry can be used in a simultaneous cyclization/deprotection reaction between selenocysteine and cysteine residues protected by p-methoxybenzyl groups to form a selenylsulfide bond, demonstrating future high utility of the deprotection method. Copyright (c) 2006 European Peptide Society and John Wiley & Sons, Ltd.