Chemical modification articles within Nature Communications

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  • Article
    | Open Access

    Ligand discovery against membrane proteins has been a major challenge, mainly due to the peculiar nature of their natural habitat. Here, the authors designed a new chemical proteomic probe that targets the lysines exposed on the cell surface and developed a chemical proteomic strategy for global analysis of surface functionality in living cells.

    • Ting Wang
    • , Shiyun Ma
    •  & Haojie Lu

  • Article
    | Open Access

    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

  • Article
    | Open Access

    The combination of a covalent electrophile with a peptide or protein-based scaffold enables the targeting of shallow protein surfaces, but the approaches to convert native peptide sequences into covalent binders are missing. Here, the authors report the design of protein-based thiomethacrylate ester electrophiles that can be installed on unprotected peptides and proteins via cysteine side chains and react efficiently and selectively with cysteine and lysine side chains on the target.

    • Ronen Gabizon
    • , Barr Tivon
    •  & Nir London

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Chemical catalysts that can promote physiologically important post-translational modifications acting as enzyme surrogates have not been reported. Here, the authors develop mBnA, a chemical catalyst that promotes histone lysine acylation in live cells by activating endogenous acyl-CoAs as the only acyl donors.

    • Misuzu Habazaki
    • , Shinsuke Mizumoto
    •  & Motomu Kanai

  • Article
    | Open Access

    Peptide-based therapeutics are promising therapeutic modalities, however, their prevalent drawback is poor circulation half-life in vivo. Here, the authors report the selection of albumin-binding macrocyclic peptides from genetically encoded libraries of peptides modified by perfluoroaryl-cysteine chemistry, with decafluoro-diphenylsulfone.

    • Jeffrey Y. K. Wong
    • , Arunika I. Ekanayake
    •  & Ratmir Derda

  • Article
    | Open Access

    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

  • Article
    | Open Access

    Histone acetylation activates gene transcription but its direct read/write mechanism is unknown. Here the authors show by cryo-electron microscopy that p300/CBP reads acetylation at histone H4 and writes it to other histones in the nucleosome.

    • Masaki Kikuchi
    • , Satoshi Morita
    •  & Takashi Umehara

  • Article
    | Open Access

    Homogeneous engineering of proteins is promising to study biological functions and for the development of therapeutic conjugates. Here, the authors report a one-pot multicomponent Furan-Thiol-Amine reaction for diverse applications, including labelling of peptides, synthesis of macrocyclic and stapled peptides, selective modification of different proteins with varying payloads, and labelling of lysine and cysteine in a complex human proteome.

    • Yuwen Wang
    • , Patrick Czabala
    •  & Monika Raj

  • Article
    | Open Access

    Naturally occurring peptides with high membrane permeability often have backbone ester bonds. Here, the authors investigated the effect of an amide-to-ester substitution on membrane permeability of peptides and found the substitution is useful for improving membrane permeability of cyclic peptides.

    • Yuki Hosono
    • , Satoshi Uchida
    •  & Shinsuke Sando

  • Article
    | Open Access

    The enzyme ATE1 catalyzes eukaryotic post-translation arginylation, a key protein modification necessary for cellular homeostasis. Here, the authors show that ATE1s are previously unrealized iron-sulfur proteins that use this oxygen-sensitive inorganic cofactor to control cellular arginylation

    • Verna Van
    • , Janae B. Brown
    •  & Aaron T. Smith

  • Article
    | Open Access

    Natural adhesives have received a lot of attention recently. Here, the authors develop a natural biological adhesive from snail mucus that can adhere to wet tissue and be used to accelerate healing of skin wounds.

    • Tuo Deng
    • , Dongxiu Gao
    •  & Mingyi Wu

  • Article
    | Open Access

    Transplantation of helpful bacteria has been used to treat disease through modulating host microbiota. Here, the authors report a strategy to control bacteria localization in the jejunum, via an in vivo in-situ thiol-disulfide exchange reaction between surface-reactive bacteria and mucous.

    • Huilong Luo
    • , Yanmei Chen
    •  & Jinyao Liu

  • Article
    | Open Access

    The characterization of lysine lactylation (Kla) in prokaryotes remains unclear. Here, the authors identify the regulatory enzymes (YiaC as a lactylase and CobB as a delactylase) and functional network of Kla and reveal a Kla-mediated molecular mechanism for glycolysis regulation in Escherichia coli.

    • Hanyang Dong
    • , Jianji Zhang
    •  & Kai Zhang

  • Article
    | Open Access

    Controlling the selectivity of the chemical modification of a genetic-manipulation-free protein is currently problematic. Here the authors report a method using cysteine-based chemoselective Linchpin Directed site-selective Modification of the lysine residue in a protein.

    • Neelesh C. Reddy
    • , Rajib Molla
    •  & Vishal Rai

  • Article
    | Open Access

    Sun et al. has studied the genetically encodable halotyrosines in proteins of the prokaryotic cell division machinery to elucidate the general role of halogenation in cellular lifespan and oxidative damage-induced diseases such as aging and cancer.

    • Huan Sun
    • , Haiyang Jia
    •  & Nediljko Budisa

  • Article
    | Open Access

    tag-Targeted Protein Degrader (tTPD) systems are powerful tools for preclinical target validation. Here the authors extend the tTPD platform by developing NanoTACs that degrade NanoLuc tagged substrates and benchmark each tTPD system using an interchangeable tag reporter system.

    • Christoph Grohmann
    • , Charlene M. Magtoto
    •  & Rebecca Feltham

  • Article
    | Open Access

    Strategies capable of stapling unprotected peptides in a straightforward, chemoselective, and clean manner, as well as promoting cellular uptake are of great interest. Here the authors report a peptide macrocyclization and stapling strategy which satisfies those criteria, based on a fluorine thiol displacement reaction.

    • Md Shafiqul Islam
    • , Samuel L. Junod
    •  & Rongsheng E. Wang

  • Article
    | Open Access

    A major question in redox signaling is how H2O2 oxidizes target protein thiols in the presence of glutathione peroxidases and peroxiredoxins. We reveal signaling by H2O2 via its enzymatic conversion to an alkyl hydroperoxide that stereo-specifically escapes peroxidases and oxidizes target proteins.

    • Raphael F. Queiroz
    • , Christopher P. Stanley
    •  & Roland Stocker

  • Article
    | Open Access

    An upregulation of NSD2, a histone H3 lysine 36 (H3K36) methyltransferase is linked to multiple myeloma and other types of cancer. Here, the authors provide insights into the regulatory mechanism of NSD2 by determining the 2.8 Å cryo-EM structure of the NSD2 bound nucleosome complex, and based on MD simulations they discuss how two oncogenic mutations enhance NSD2 activity.

    • Ko Sato
    • , Amarjeet Kumar
    •  & Toru Sengoku

  • Article
    | Open Access

    Development of Cas12a for human therapeutics and diagnostics may significantly benefit from, or even require, chemical modification of its guide RNA. Here the authors show that the noncanonical 5′ pseudoknot structure of the AsCas12a crRNA guide can be heavily modified and still retain very high editing activity in cells and trans cleavage activity in vitro.

    • Eman A. Ageely
    • , Ramadevi Chilamkurthy
    •  & Keith T. Gagnon

  • Article
    | Open Access

    Heterotopic ossification (HO) is the formation of pathological mature bone within extraskeletal soft tissues, and there are currently no reliable methods for removing these calcified plaques. Here, the authors demonstrate that chemically engineered osteoclasts coated with tetracycline can improve their targeting capacity to ectopic calcifications, which extends their bone resorption functions for the treatment of HO.

    • Wenjing Jin
    • , Xianfeng Lin
    •  & Ruikang Tang

  • Article
    | Open Access

    The mechanism-of-action of many electrohilic drugs remains poorly understood. Here, the authors use a redox-targeting approach to elucidate the basis for the innate immune cell toxicity of dimethyl fumarate, showing that it modifies Keap1 to trigger mitochondrial-targeted neutrophil/macrophage apoptosis.

    • Jesse R. Poganik
    • , Kuan-Ting Huang
    •  & Yimon Aye

  • Article
    | Open Access

    Analogues of α-ketoglutarate are used in many cellular studies but assumptions are made about cellular uptake. Here, the authors show that esterified analogues rapidly hydrolyse in aqueous medium resulting in an analogue which can be quickly taken up by many cell lines, contrary to prevailing assumptions.

    • Seth J. Parker
    • , Joel Encarnación-Rosado
    •  & Alec C. Kimmelman

  • Article
    | Open Access

    STAT1a is required for pro-inflammatory responses in macrophages. Here the authors reveal that post-translational modification of STAT1a, ADPribosylation, plays a critical role in enhancer formation and activation, thus modulating IFNγ-stimulated inflammatory responses in macrophages.

    • Rebecca Gupte
    • , Tulip Nandu
    •  & W. Lee Kraus

  • Article
    | Open Access

    Advanced glycation end-products (AGEs), such as methylglyoxal-derived hydroimidazolone isomer (MGH-1), are associated with disease and age-related disorders, and occur spontaneously, so it is unclear why specific protein sites become modified with specific AGEs. Here, the authors use a combinatorial peptide library to determine the chemical features that favour MGH-1 formation for short peptides and demonstrate a key role of tyrosine in this process.

    • Joseph M. McEwen
    • , Sasha Fraser
    •  & Rebecca A. Scheck

  • Article
    | Open Access

    Methods for selective modification of the N-terminus of proteins are of high interest, but mostly require specific amino acid residues. Here, the authors report a selective and fast method for N-terminal modification of proteins based on quinone-mediated oxidation of the alpha-amine to aldehyde or ketone, and apply it to diverse proteins.

    • Siyao Wang
    • , Qingqing Zhou
    •  & Ping Wang

  • Article
    | Open Access

    Investigation of spatial organization and relationships of biomolecules in cellular nanoenvironments is necessary to understand essential biological processes, but methodologically challenging. Here, the authors report cellular macromolecules-tethered DNA walking indexing (Cell-TALKING) to probe the nanoenvironments of DNA modifications around histone post-translational modifications, and explore the nanoenvironments in different cancer cell lines and clinical specimens.

    • Feng Chen
    • , Min Bai
    •  & Yongxi Zhao

  • Article
    | Open Access

    The analysis of AMPA-type glutamate receptor (AMPAR) trafficking is essential for understanding molecular mechanisms of learning and memory, but the analytical tools are currently limited. Here, the authors report a method that combines affinity-based receptor labeling and bioorthogonal click chemistry to quantify AMPAR distribution and trafficking under physiological conditions.

    • Kento Ojima
    • , Kazuki Shiraiwa
    •  & Shigeki Kiyonaka

  • Article
    | Open Access

    Covalent conjugation of endogenous protein complexes offers many opportunities for fundamental and clinical research. Based on a bacterial protein domain that forms a reactive anhydride in the presence of Ca2+, the authors here develop a system that enables the covalent capture of endogenous binding partners.

    • Arne H. A. Scheu
    • , Sheryl Y. T. Lim
    •  & Mark Howarth

  • Article
    | Open Access

    Mitochondrial oxidation-induced cell death is an important physiological process activated by cancer therapeutics, but its investigation is challenging. Here, the authors report a multifunctional iridium(III) photosensitiser, Ir-OA, able to induce mitochondrial oxidative stress and monitor the corresponding changes in mitochondrial properties.

    • Chaiheon Lee
    • , Jung Seung Nam
    •  & Tae-Hyuk Kwon

  • Article
    | Open Access

    KEOPS is an evolutionary conserved complex with a core of four core subunits—Pcc1, Kae1, Bud32 and Cgi121—that catalyzes the universal and essential tRNA modification N6-threonylcarbamoyl adenosine (t6A). Here the authors describe a Cgi121-tRNA crystal structure and new composite model of the KEOPS holo-enzyme-substrate complex that shed light on the t6A catalytic cycle and its regulation.

    • Jonah Beenstock
    • , Samara Mishelle Ona
    •  & Frank Sicheri

  • 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

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