Bioinspired Nitroalkylation for Selective Protein Modification and Peptide Stapling.,Angewandte Chemie International Edition

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Bioinspired Nitroalkylation for Selective Protein Modification and Peptide Stapling.
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2019-11-27 , DOI: 10.1002/anie.201908593
Sriram Mahesh ₁ , Victor Adebomi ₁ , Zilma P Muneeswaran ₂ , Monika Raj ₁

Affiliation

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 19 F NMR spectroscopy. Furthermore, nitroalkane reagents can be used for the late-stage diversification of peptides and for the synthesis of peptide staples.

中文翻译：

生物启发的硝基烷基化用于选择性蛋白质修饰和肽钉合。

硝基烷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结合。这些硝基烷基化的蛋白质模拟蛋白质的关键翻译后修饰（PTM），可用于了解这些PTM在细胞过程中的作用。这里通过将各种标签（例如NMR标签，荧光标签，亲和标签和炔烃标签）附着到蛋白质上来说明这种生物共轭的底物范围。标记后，修饰蛋白的结构和酶活性保持保守。值得注意的是，由于硝基烷烃基团具有独特的指纹图谱，因此可通过质谱法轻松表征蛋白质。重要的是，硝基烷基化的肽为肽的位点选择性氟化提供了新的方法，因此，通过19 F NMR光谱法安装了特异性探针来研究肽-蛋白质相互作用。此外，硝基烷试剂可用于肽的后期多样化和肽钉的合成。

更新日期：2020-01-16

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