Chemical modification articles within Nature Communications

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  • Article
    | Open Access

    For almost forty years, N-(1-pyrene) iodoacetamide has been used to label actin at C374, but the mechanisms of the fluorescence changes are still unknown due to the lack of structural information. Here authors provide cryo-EM structures of actin filaments with N-1-pyrene conjugated to cysteine 374 and either ADP or ADP-phosphate in the active site.

    • Steven Z. Chou
    •  & Thomas D. Pollard

  • Article
    | Open Access

    ADP-ribosylated peptides are important molecular tools, however, the lack of effective synthetic methods hinders the access to their complex structures. Here, the authors present a biomimetic α-selective ribosylation reaction coupled with click chemistry ultimately providing a two-step modular synthesis of α-ADP-ribosylated peptides.

    • Anlian Zhu
    • , Xin Li
    •  & Lingjun Li

  • Article
    | Open Access

    Developing new click chemistry reactions for robust molecular assembly remains challenging. Here the authors report a light-induced primary amines and o-nitrobenzyl alcohols photoclick cyclization for rapid and modular functionalization of small molecules and native biomolecules, in vitro and in living systems.

    • An-Di Guo
    • , Dan Wei
    •  & Xiao-Hua Chen

  • Article
    | Open Access

    Uncontrolled gene editing can lead to off-target effects and chromosomal translocations. Here the authors develop CRISPRoff, light degradable sgRNAs for titratable and spatially defined gene editing.

    • Jared Carlson-Stevermer
    • , Reed Kelso
    •  & Travis Maures

  • Article
    | Open Access

    Protein tyrosine O-sulfation is crucial for biomolecular interactions. Here the authors report in vitro engineering and in vivo validation of a tyrosyl-tRNA synthetase mutant for the genetic encoding of sulfotyrosine in mammalian cells.

    • Xinyuan He
    • , Yan Chen
    •  & Wei Niu

  • Article
    | Open Access

    5-hydroxythalidomide is a primary thalidomide metabolite generated by the cytochrome P450 isozymes. The reported data, including crystal structure of the 5-hydroxythalidomide-mediated complex of CRBN with SALL4, elucidate how additional hydroxy group of the metabolite enhances the interaction of CRBN with the neosubstrate SALL4.

    • Hirotake Furihata
    • , Satoshi Yamanaka
    •  & Takuya Miyakawa

  • Article
    | Open Access

    Control of cysteine reactivity is of paramount importance for the synthesis of proteins using native chemical ligation. Here, the authors report a readily cleavable N-selenoethyl group attached to cysteine and apply it to the modular assembly of linear and cyclic polypeptides.

    • Vincent Diemer
    • , Nathalie Ollivier
    •  & Oleg Melnyk

  • Article
    | Open Access

    N-terminal glycine myristoyl transferases (NMTs) catalyse the myristoylation of eukaryotic proteins. Here, the authors provide insights into the catalytic mechanism of NMTs by determining the crystal structures of human NMT1 in complex with reactive cognate lipid and peptide substrates and further show that NMT1 also catalyses the acylation of N-terminal lysines.

    • Cyril Dian
    • , Inmaculada Pérez-Dorado
    •  & Carmela Giglione

  • Article
    | Open Access

    Cystine-knot miniprotein are small, highly stable, disulfide-rich peptides with increasing potential as drugs and tumor imaging agents. Here the authors develop cystine-knot miniproteins targeting the vascular tumor marker EDB, and use them as probes for in vivo tumor vasculature imaging.

    • Bonny Gaby Lui
    • , Nadja Salomon
    •  & Ugur Sahin

  • Article
    | Open Access

    Bacterial tRNA is modified by thiolation of nucleosides. Here the authors identify 2-methylthiocytidine in bacterial tRNA using nucleic acid isotope labeling coupled mass spectrometry. Exposure to methylating agents converts 2-thiocytidine to 2-methylthiocytidine, which is repaired by demethylase AlkB in vivo.

    • Valentin F. Reichle
    • , Dimitar P. Petrov
    •  & Stefanie Kellner

  • Article
    | Open Access

    Membrane-anchored DNA probes have been used to study molecular interactions and control cell assembly, but are not selective for different cell membranes. Here the authors develop a lipid-conjugated oligonucleotide for alkaline phosphatase-dependent cell membrane anchorage and use it to distinguish different cancer cells.

    • Cheng Jin
    • , Jiaxuan He
    •  & Weihong Tan

  • Article
    | Open Access

    Single-site labelling of proteins is desirable, e.g., for analytical purposes. Here, the authors developed a method in which they use an aldol-type reaction to modify proteins at N-terminal glycine residues in an efficient and selective manner, which is also applicable to cell lysates.

    • Landa Purushottam
    • , Srinivasa Rao Adusumalli
    •  & Vishal Rai

  • Article
    | Open Access

    The selective formation of protein bioconjugates under physiological conditions is a challenging task. Here, the authors report that 1,4-dinitroimidazoles are reagents of choice for protein bioconjugation at either cysteine or lysine sites within short times and provide facile access to peptide macrocycles.

    • Qunfeng Luo
    • , Youqi Tao
    •  & Huan Wang

  • Article
    | Open Access

    MLL3 and MLL4 are members of the SET1/MLL family of histone H3K4 methyltransferases, which are responsible for monomethylating histone H3K4 on enhancers. Here the authors show that an extended PHD domain (ePHD6) in MLL3 and MLL4 specifically recognizes an H4H18-containing fragment of histone H4, and that modifications of residues surrounding H4H18 modulate H4 binding to MLL3/4.

    • Yanli Liu
    • , Su Qin
    •  & Jinrong Min

  • Article
    | Open Access

    The recognition of the mRNA codon by the tRNA anticodon is crucial for protein synthesis. Here the authors introduce non-standard nucleotides in bacterial and eukaryotic mRNA to reveal the minimal hydrogen bond requirement of codon-anticodon interaction for efficient and accurate translation.

    • Thomas Philipp Hoernes
    • , Klaus Faserl
    •  & Matthias David Erlacher

  • Article
    | Open Access

    His-tagged proteins can undergo N-terminal acylation as an undesired side-reaction. Here, the authors utilize this to develop a method for highly selective acylation and further modification of peptides and proteins using an optimized His sequence and 4-methoxyphenyl esters as acyl donors.

    • Manuel C. Martos-Maldonado
    • , Christian T. Hjuler
    •  & Knud J. Jensen

  • Article
    | Open Access

    Carbon dioxide can interact with proteins to form carbamate post-translational modifications. Here, the authors developed a strategy to identify carbamate post-translational modifications by trapping carbon dioxide and subsequently identifying the carbamylated proteins.

    • Victoria L. Linthwaite
    • , Joanna M. Janus
    •  & Martin J. Cann

  • Article
    | Open Access

    Retention of drugs loaded into liposomes is a major challenge to effective targeted drug delivery. Here, the authors report on the modification of drugs with a glycosidic pH sensitive switch to improve encapsulation and retention of drugs and demonstrate application in an in vivo cancer model.

    • Pierre-Alain Burnouf
    • , Yu-Lin Leu
    •  & Steve R. Roffler

  • Article
    | Open Access

    Tools to investigate a wide range of 3D microenvironmental parameters are important for understanding and controlling cell fate. Here, the authors develop hydrogels with orthogonal biochemical gradients and use this screening system to identify microenvironments that induce mesenchymal stem cell chondrogenesis.

    • Sebastián L. Vega
    • , Mi Y. Kwon
    •  & Jason A. Burdick

  • Article
    | Open Access

    Current ART for treatment of HIV-1 infection requires a strict daily regimen adherence. Herein, the authors report the manufacture and characterization of a nanoformulated dolutegravir prodrug with improved cell and tissue penetration, a remarkable apparent half-life and the potential for bimonthly drug administration.

    • Brady Sillman
    • , Aditya N. Bade
    •  & Howard E. Gendelman

  • Article
    | Open Access

    Visualizing neurotransmitter receptor traffic is fundamental to understanding brain functions, but the current imaging methods can compromise the process. Here, the authors synthesize small fluorescent probes to label endogenous glutamate receptors in cell cultures and brain tissues, without affecting their function.

    • Sho Wakayama
    • , Shigeki Kiyonaka
    •  & Itaru Hamachi

  • Article
    | Open Access

    Diphtheria toxin selectively kills cells engineered to express the diphtheria toxin receptor (DTR). Here the authors report a PEGylated version of diphtheria toxin that does not enter the brain, allowing for ablation of only peripheral cells when using Cre lines that drive DTR expression in both the periphery and in the brain.

    • Mafalda M. A. Pereira
    • , Inês Mahú
    •  & Ana I. Domingos

  • Article
    | Open Access

    Current cysteine bioconjugation strategies for protein-drug conjugates synthesis often yield heterogeneous and poorly stable products. Here, the authors use carbonylacrylic derivatives to selectively modify cysteine residues and synthesize biologically functional antibody conjugates highly stable in plasma.

    • Barbara Bernardim
    • , Pedro M.S.D. Cal
    •  & Gonçalo J. L. Bernardes

  • Article
    | Open Access

    DNA 6mA is a poorly understood epigenetic mark present at a low abundance in eukaryotic genomes. Here the authors observe high levels in zebrafish and pig during early embryogenesis enriched to repetitive regions of the genome and followed by attenuation during development.

    • Jianzhao Liu
    • , Yuanxiang Zhu
    •  & Chuan He

  • Article
    | Open Access

    Chemical approaches to site-specifically ubiquitylate a target protein allow investigation of the biochemical effects of this modification, but they often destabilize the protein. Here, the authors report on a synthetic conjugation strategy that leads to protein ubiquitylation in non-denaturing conditions.

    • Caroline E. Weller
    • , Abhinav Dhall
    •  & Champak Chatterjee

  • Article
    | Open Access

    Succinimide is a post-translational modification susceptible to rapid hydrolysis and generally associated with protein destabilisation. Here, the authors use mass spectroscopy to identify a stable succinimide intermediate that is responsible for the high thermostability of a thermophilic enzyme.

    • Sanjeev Kumar
    • , Sunita Prakash
    •  & Hemalatha Balaram

  • Article
    | Open Access

    Protein phosphorylation mediates signalling and other important cellular processes, but the specific effect of cysteine phosphorylation is unclear. Here, the authors present a chemical strategy to selectively phosphorylate cysteine residues and a mass spectrometry approach to detect and characterize endogenous pCys sites.

    • Jordi Bertran-Vicente
    • , Martin Penkert
    •  & Christian P. R. Hackenberger

  • Article
    | Open Access

    The response to hypoxia involves multiple genes regulated by the hypoxia inducible transcription factors (HIFs), whose stability is regulated by prolyl hydroxylation. Here the authors provide a molecular basis for the substrate selectivity of the HIF prolyl hydroxylases that can be altered in erythrocytosis and cancer.

    • Rasheduzzaman Chowdhury
    • , Ivanhoe K. H. Leung
    •  & Christopher J. Schofield

  • Article
    | Open Access

    Peptide and oligonucleotide systems are known to self-assemble both in nature and artificial systems. Here, the authors combine both forms of self-assembly through the synthesis of peptideoligonucleotide conjugates and show formation of a three-helix structure that dimerises at higher concentrations.

    • Chenguang Lou
    • , Manuel C. Martos-Maldonado
    •  & Knud J. Jensen

  • Article
    | Open Access

    A structurally diverse set of epigenetic reader proteins can recognize methylated lysine residues on histones. Here the authors show that recognition of trimethyllysine occurs through a combination of favourable cation–πinteractions and the release of water molecules occupying the aromatic cages of reader proteins.

    • Jos J.A.G. Kamps
    • , Jiaxin Huang
    •  & Jasmin Mecinović

  • Article
    | Open Access

    Amyloid assemblies lie at the heart of many physiological functions, as well as being the cause of numerous diseases. Here, the authors subtly modify wild-type pentapeptides with halides, and discover that the new halogen bonding interactions have a remarkable influence on their physical properties.

    • Arianna Bertolani
    • , Lisa Pirrie
    •  & Pierangelo Metrangolo

  • Article |

    Acyldepsipeptides are natural antibiotics that function by activating the ClpP protease and deregulating proteolysis. Here, Gersch et al.show that acyldepsipeptides not only increase access to the active sites but also exert conformational control, thereby allosterically stimulating ClpP catalysis.

    • Malte Gersch
    • , Kirsten Famulla
    •  & Stephan A. Sieber

  • Review Article |

    The chemical modification of proteins is an important tool for probing natural systems and synthesizing novel conjugates. Here, Spicer and Davis review the merits and limitations of the most useful methods for selective modification at both natural and unnatural amino acids.

    • Christopher D. Spicer
    •  & Benjamin G. Davis

  • Article |

    Short interfering siRNAs—siRNAs—have therapeutic potential in the treatment of disease; however, their delivery to target tissues is difficult. Here, Wu et al. chemically modify siRNAs and show that this improves loading into the siRNA silencing machinery and thus efficacy in eliminating cancer cells in mice.

    • Sherry Y. Wu
    • , Xianbin Yang
    •  & Anil K. Sood

  • Article
    | Open Access

    Aminoglycoside antibiotics target the ribosome but their limited selectivity for the bacterial ribosome can cause side effects in humans. Here, the authors synthesize 4′-O-ether or 4′,6′-O-acetal modifications and show that these compounds possess increased selectivity against bacterial ribosomes.

    • Déborah Perez-Fernandez
    • , Dmitri Shcherbakov
    •  & Erik C. Böttger

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