Of all the commercially available amino acid derivatives for solid phase peptide synthesis, none has a greater abundance of side‐chain protection diversity than cysteine. The high reactivity of the cysteine thiol necessitates its attenuation during peptide construction. Moreover, the propensity of cysteine residues within a peptide or protein sequence to form disulfide connectivity allows the opportunity for the peptide chemist to install these disulfides iteratively as a post‐synthetic manipulation through the judicious placement of orthogonal pairs of cysteine S‐protection within the peptide's architecture. It is important to continuously discover new vectors of deprotection for these different blocking protocols in order to achieve the highest degree of orthogonality between the removal of one species in the presence of another. We report here a complete investigation of the scope and limitations of the deprotective potential of 2,2′‐dithiobis(5‐nitropyridine) (DTNP) on a selection of commercially available Cys S‐protecting groups. The gentle conditions of DTNP in a TFA solvent system show a remarkable ability to deprotect some cysteine blocking functionality traditionally removable only by more harsh or forcing conditions. Beyond illustrating the deprotective ability of this reagent cocktail within a cysteine‐containing peptide sequence, the utility of this method was further demonstrated through iterative disulfide formation in oxytocin and apamin test peptides. It is shown that this methodology has high potential as a stand‐alone cysteine deprotection technique or in further manipulation of disulfide architecture within a more complex cysteine‐containing peptide template. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.

中文翻译：

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2,2'-二硫代双(5-硝基吡啶) (DTNP) 作为常见半胱氨酸保护基团的有效且温和的脱保护剂。

在用于固相肽合成的所有市售氨基酸衍生物中，没有一种比半胱氨酸具有更丰富的侧链保护多样性。半胱氨酸硫醇的高反应性使其在肽构建过程中需要衰减。此外，肽或蛋白质序列中的半胱氨酸残基倾向于形成二硫键连接，这使肽化学家有机会通过在肽段内的半胱氨酸 S 保护的正交对的明智放置来迭代地安装这些二硫键，作为合成后的操作。建筑学。为这些不同的阻断方案不断发现新的去保护载体是很重要的，以便在一个物种的去除与另一种物种的去除之间实现最高程度的正交性。我们在此报告了对 2,2'-二硫代双（5-硝基吡啶）（DTNP）在一系列市售 Cys S 保护基团上的脱保护潜力的范围和局限性的完整调查。DTNP 在 TFA 溶剂系统中的温和条件显示出非凡的能力，可以对某些传统上只能通过更苛刻或强制条件去除的半胱氨酸封闭功能进行去保护。除了说明该试剂混合物在含半胱氨酸的肽序列中的去保护能力之外，该方法的实用性还通过在催产素和阿巴胺测试肽中反复形成二硫键进一步证明。结果表明，该方法作为独立的半胱氨酸脱保护技术或在更复杂的含半胱氨酸肽模板中进一步操作二硫键结构具有很高的潜力。版权所有 © 2011 欧洲肽学会和 John Wiley & Sons, Ltd.