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Design and synthesis of cysteine-specific labels for photo-crosslinking studies

机译:设计和合成用于光交联研究的半胱氨酸特异性标记

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Chemical cross-linking mass-spectrometry (XL-MS) represents a powerful methodology to map ligand/biomacromolecule interactions, particularly where conventional methods such as X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy or cryo-electron microscopy (EM) are not feasible. In this manuscript, we describe the design and synthesis of two new photo-crosslinking reagents that can be used to specifically label free thiols through either maleimido or methanethiosulfonate groups and facilitate PXL-MS workflows. Both crosslinkers are based on light sensitive diazirines – precursors of highly reactive carbenes which offer additional advantages over alternative crosslinking groups such as benzophenones and aryl nitrenes given the controlled rapid and more indiscriminate reactivity.
机译:化学交联质谱(XL-MS)是绘制配体/生物大分子相互作用图的有力方法,尤其是在常规方法(例如X射线晶体学,核磁共振(NMR)光谱或低温电子显微镜(EM))的情况下不可行。在本手稿中,我们描述了两种新的光交联剂的设计和合成,这些试剂可用于通过马来酰亚胺基或甲硫基磺酸盐基团特异性标记游离硫醇,并促进PXL-MS工作流程。两种交联剂均基于对光敏感的二嗪,这是高反应性卡宾的前体,鉴于可控的快速反应和不加区分的反应性,与替代的交联基团(如二苯甲酮和芳基腈)相比,它们具有更多的优势。

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