Bioinspired Nitroalkylation for Selective Protein Modification and Peptide Stapling
Bioinspired Nitroalkylation for Selective Protein Modification and Peptide Stapling
复制标题
DOI：
10.1002/anie.201908593
复制
发表时间：
2020-01-16
影响因子：
16.6
通讯作者：
Raj, Monika
中科院分区：
文献类型：
--
作者：
Mahesh, Sriram;Adebomi, Victor;Raj, Monika
硝基烷烃与醛发生特异性反应，提供快速、稳定和化学选择性的蛋白质生物偶联。这些硝基烷基化蛋白模拟蛋白质的关键翻译后修饰（PTMs），可用于了解这些PTMs在细胞过程中的作用。这里展示的是这种生物偶联的底物范围，通过将各种标签，如核磁共振标签、荧光标签、亲和标签和炔标签附加到蛋白质上。标记后的修饰蛋白结构和酶活性保持保守。值得注意的是，硝基烷烃基团由于其独特的指纹图谱而易于通过质谱法表征蛋白质。重要的是，硝基烷基化多肽为多肽的位点选择性氟化提供了一个新的处理方法，从而安装了一个特定的探针，通过F-19核磁共振光谱研究多肽-蛋白质相互作用。此外，硝基烷烃试剂可用于肽的后期多样化和肽钉的合成。
Nitroalkanes react specifically with aldehydes, providing rapid, stable, and chemoselective protein bioconjugation. These nitroalkylated proteins mimic key post-translational modifications (PTMs) of proteins and can be used to understand the role of these PTMs in cellular processes. Demonstrated here is the substrate scope of this bioconjugation by attaching a variety of tags, such as NMR tags, fluorescent tags, affinity tags, and alkyne tags, to proteins. The structure and enzymatic activity of modified proteins remain conserved after labeling. Notably, the nitroalkane group leads to easy characterization of proteins by mass spectrometry because of its distinct fingerprint pattern. Importantly, the nitro-alkylated peptides provide a new handle for site-selective fluorination of peptides, thus installing a specific probe to study peptide-protein interactions by F-19 NMR spectroscopy. Furthermore, nitroalkane reagents can be used for the late-stage diversification of peptides and for the synthesis of peptide staples.