Chemical modification of proteins

Articles

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  Chemoselective dual functionalization of proteins via 1,6-addition of thiols to trifunctional N-alkylpyridinium

  Chemoselective dual functionalization of proteins is an invaluable tool to introduce two distinct payloads to proteins. Here, the authors present N-alkylpyridinium reagents as soft electrophiles for chemoselective dual modification of cysteine residues in peptides or proteins via a 1,6-addition reaction.

  • Lujuan Xu
  • Maria J. S. A. Silva
  • Tanja Weil

  ArticleOpen Access6 Jun 2025 Nature Communications
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  Coarctate reaction for synthesis of fluorescent N-heterocycles, late-stage functionalization, and photo-triggered drug delivery

  Coarctate reactions, involving the simultaneous formation and cleavage of two bonds at single or multiple atoms, have remained largely unexplored for biomolecular applications. Here, the authors use an azo-ene-yne coarctate reaction to synthesize isoindazole-based N-heterocycles and explore their applications in the synthesis of unnatural amino acids and drug conjugates, and late-stage peptide functionalization.

  • Samrat Sahu
  • Zachary E. Paikin
  • Monika Raj

  ArticleOpen Access22 Apr 2025 Nature Communications
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  Copper assisted sequence-specific chemical protein conjugation at a single backbone amide

  Direct, site-specific methods of protein functionalization are of interest, but challenging due to difficulty in chemically differentiating a single site within a large protein. Here, the authors develop a Copper Assisted Sequence-specific conjugation Tag (CAST) method to achieve rapid, site-specific protein backbone chemical modification with pinpoint accuracy, and prepare various on-demand modified recombinant proteins using CAST.

  • Mengzhun Guo
  • Kai Zhao
  • Bobo Dang

  ArticleOpen Access5 Dec 2023 Nature Communications
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  C-terminal modification and functionalization of proteins via a self-cleavage tag triggered by a small molecule

  Specific modification or functionalization of proteins at the C-terminus is of interest but remains challenging. Here, the authors report an approach for the efficient modification of C-terminus by fusion of the cysteine protease domain (CPD) on the C-terminus of the protein of interest, and subsequent functionalization with amine-containing molecules triggered by InsP6-mediated CPD self-cleavage.

  • Yue Zeng
  • Wei Shi
  • Feng Tang

  ArticleOpen Access7 Nov 2023 Nature Communications
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  Click-electrochemistry for the rapid labeling of virus, bacteria and cell surfaces

  Methods for direct covalent ligation of microorganism surfaces are scarce. Here, the authors developed a rapid electrochemical process for the direct covalent ligation and labelling of the surfaces of virus, bacteria and cells using N-methylluminol, a fully tyrosine-selective protein anchoring group.

  • Sébastien Depienne
  • Mohammed Bouzelha
  • Sébastien G. Gouin

  ArticleOpen Access23 Aug 2023 Nature Communications
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  Modular synthesis of clickable peptides via late-stage maleimidation on C(7)-H tryptophan

  Cyclic peptides are of interest due to their application in pharmaceutical industry, but currently there are limited methodologies for their synthesis. Here, the authors report an efficient and direct peptide cyclization via rhodium(III)-catalysed C(7)-H maleimidation.

  • Peng Wang
  • Jiang Liu
  • Yuguo Zheng

  ArticleOpen Access5 Jul 2023 Nature Communications
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  Catalyst-free late-stage functionalization to assemble α-acyloxyenamide electrophiles for selectively profiling conserved lysine residues

  Covalent probes are a powerful tool for investigating small molecule and protein interactions, however, the development of reactive warheads to form covalent probes remains underexplored. Here, the authors develop α-acyloxyenamide electrophiles to covalently bind to lysine residues, and selectively profile the conserved lysine residues of kinase in live cells.

  • Yuanyuan Zhao
  • Kang Duan
  • Zhengqiu Li

  ArticleOpen Access14 Feb 2024 Communications Chemistry
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  Nucleotide-mediated modulation of chemoselective protein functionalization in a liquid-like condensed phase

  Liquid-like protein condensates are ubiquitous in cellular systems and play key roles in physiological processes, with the condensed phase harboring a distinctive chemical microenvironment. Here, the authors systematically investigate how the local chemical environment within protein condensates impacts chemical reactivity, demonstrating nucleotide-mediated modulation of chemoselective protein functionalization.

  • Nandha Kumar Ettikkan
  • Priyanka Priyanka
  • Subhabrata Maiti

  ArticleOpen Access26 Oct 2024 Communications Chemistry
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  Single electron transfer-based peptide/protein bioconjugations driven by biocompatible energy input

  Photochemical and electrochemical approaches to protein and peptide modification offer a valuable complement to the use of stoichiometric reagents. Here recent developments in bioconjugation methodology relying on single electron transfer are described.

  • Yue Weng
  • Chunlan Song
  • Aiwen Lei

  PerspectiveOpen Access13 Nov 2020 Communications Chemistry
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  Vinyl thianthrenium-mediated cysteine bioconjugation

  Covalent cysteine labeling is an important tool in protein modification, however, current methodologies suffer from limited reactivities and require the prior synthesis of individual derivative reagents. Now, a covalent cysteine labeling method that converts the cysteinyl thiol into episulfonium electrophiles in situ has been developed, enabling reactions with various nucleophiles in one step.

  • Huijuan Guo

  Research HighlightOpen Access27 Feb 2024 Communications Chemistry