Peptides articles within Nature Communications

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  • Article
    | Open Access

    Prodrugs have the potential for improving therapeutic index and expanding drug targets, but current prodrug activation strategies that are responsive to endogenous stimuli can result in unintended drug release and systemic toxicity. Here, the authors report 3-vinyl−6-oxymethyltetrazine (voTz) as an all-in-one reagent for modular preparation of tetrazine-caged prodrugs and chemoselective labeling of peptides to produce bioorthogonal activable peptide-prodrug conjugates.

    • Xinyu He
    • , Jie Li
    •  & Haoxing Wu

  • Article
    | Open Access

    Human leukocyte antigen (HLA) class I peptide ligands (HLAIps) are targets for developing vaccines and immunotherapies. Here the authors report Thunder-DDA-PASEF, an immunopeptidomics method which enhances the identification of vital HLAIps crucial for vaccine and immunotherapy development.

    • David Gomez-Zepeda
    • , Danielle Arnold-Schild
    •  & Stefan Tenzer

  • Article
    | Open Access

    Antimicrobial resistance is a global health threat and the development of alternative strategies to overcome it is of high interest. Here, the authors report proteolysis targeting chimeras active in bacteria (BacPROTACs) that bind to ClpC1, a component of the mycobacterial protein degradation machinery, and apply them for targeting a range of mycobacterial strains, including antibiotic-resistant ones.

    • Lukas Junk
    • , Volker M. Schmiedel
    •  & Guido Boehmelt

  • Article
    | Open Access

    Mirror-image phage display has the potential for high-throughput generation of biologically stable macrocyclic D-peptide binders but is hindered by the optimization required for D-protein chemical synthesis. Here, the authors report a general mirror-image phage display pipeline based on automated flow peptide synthesis and use it to prepare and characterize 12 L/D-protein pairs.

    • Alex J. Callahan
    • , Satish Gandhesiri
    •  & Bradley L. Pentelute

  • Article
    | Open Access

    The delivery of CRISPR RNPs has potential advantages over other genome editing approaches, including reduced off-target editing and reduced immunogenicity. Here the authors report self-deliverable Cas9 RNPs capable of robustly editing cultured cells in vitro and the mouse brain upon direct injections.

    • Kai Chen
    • , Elizabeth C. Stahl
    •  & Jennifer A. Doudna

  • Article
    | Open Access

    Here the authors use NMR, SAXS and MD simulations to characterise the structure of proteusin peptides, which are atypically long RiPP substrates. They show a small, unstructured region in the proteusin leader is sufficient for its interaction with a halogenase that brominates the terminal tryptophan residue.

    • Nguyet A. Nguyen
    • , F. N. U. Vidya
    •  & Vinayak Agarwal

  • Article
    | Open Access

    Assembly of amyloids is important in neurodegenerative diseases, but there is limited understanding of how supramolecular chirality is controlled. Here, the authors report the design of peptide derivatives that allow chirality inversion at biologically relevant temperatures.

    • Stephen J. Klawa
    • , Michelle Lee
    •  & Ronit Freeman

  • Article
    | Open Access

    Stapled α-helical peptides are promising for targeting challenging targets such as transcription factors, but achieving sufficient cell permeability while avoiding off-target cleavage is difficult. Here, the authors present workflows for identifying stapled peptides against Mdm2(X) with in vivo activity and no off-target effects based on comprehensive investigations of their properties.

    • Arun Chandramohan
    • , Hubert Josien
    •  & Anthony W. Partridge

  • Article
    | Open Access

    Peptide drug manufacturing commonly uses large amounts of hazardous solvents primarily due to multiple washings after each step. Here, the authors introduce the concept of a completely wash-free methodology that enables up to 95% waste reduction.

    • Jonathan M. Collins
    • , Sandeep K. Singh
    •  & Christopher L. Houser

  • Article
    | Open Access

    Amino acids modulate insulin secretion via amino acid transporters expressed on β cells. Here, the authors show a VGF-derived peptide NERP-4 acts as a positive allosteric modulator on the amino acid transporter SNAT2/SLC38A2, thereby contributing to β-cell maintenance and function.

    • Weidong Zhang
    • , Ayako Miura
    •  & Masamitsu Nakazato

  • Article
    | Open Access

    Protocell’s survival and fitness under prebiotic radiations are elusive. Here, the authors present a radioresistant protocell model based on the assembly of two types of coacervate droplets, formed through interactions of inorganic polyphosphate with manganese and cationic tripeptide, respectively, and show that nonenzymatic Mn antioxidants are essential for its resistance to radiation.

    • Shang Dai
    • , Zhenming Xie
    •  & Bing Tian

  • 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

    Deep learning holds a great promise for the discovery and design of bioactive peptides, but experimental approaches to validate candidates in high throughput and at low cost are needed. Here, the authors combine deep learning and cell free biosynthesis for antimicrobial peptide (AMP) development and identify 30 functional AMPs, of which six with broad-spectrum activity against drug-resistant pathogens.

    • Amir Pandi
    • , David Adam
    •  & Tobias J. Erb

  • 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

    In nature, α-helical peptides adopt right-handed conformations dictated by L-amino acids, but isolating one-handed α-helical peptides composed of only achiral components remains a challenge. Here, the authors achieve this by optical resolution of the corresponding racemic (quasi-)static α-helical peptide with double stapling, which effectively freezes the interconversion between the right-handed (P)- and left-handed (M)-α-helices.

    • Naoki Ousaka
    • , Mark J. MacLachlan
    •  & Shigehisa Akine

  • Article
    | Open Access

    Nonribosomal peptides have diverse bioactivities and can possess unusual moieties at their C-terminus, such as polyamines. In this study, the authors identify a class of dodecapeptides glidonins that feature diverse N-terminal modifications and a uniform putrescine moiety at the C-terminus, elucidate their biosynthesis, and introduce the putrescine into the C-terminus of other nonribosomal peptides.

    • Hanna Chen
    • , Lin Zhong
    •  & Xiaoying Bian

  • Article
    | Open Access

    Solvent shielding of the amide hydrogen bond donor through chemical modification or conformational control has been successfully utilized to impart membrane permeability to macrocyclic peptides. Here, the authors show that passive membrane permeability can also be conferred by masking the amide hydrogen bond acceptor through thioamide substitution, leading to improved pharmacological properties of peptide macrocycles.

    • Pritha Ghosh
    • , Nishant Raj
    •  & Jayanta Chatterjee

  • Article
    | Open Access

    The peptide/histidine transporter 1, PHT1 (SLC15A4), is required for TLR-IRF5 activation via the adaptor protein TASL. Here, the authors determined the structure of PHT1 in the outward-open conformation and present a model of the PHT1-TASL complex where the first 16 residues of TASL bind into the central cavity of PHT1.

    • Tânia F. Custódio
    • , Maxime Killer
    •  & Christian Löw

  • 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

    During solid-phase peptide synthesis (SPPS) inherent side reactions of the protected amino acids such as α-C racemization generate by-products that are hard to remove. Here, the authors report thiol-labile amino protecting group for SPPS, DNPBS group, which suppresses the main side reactions observed during conventional SPPS.

    • Yifei Zhou
    • , Hongjun Li
    •  & Chuanzheng Zhou

  • Article
    | Open Access

    Mutation associated neoantigens are a family of highly specific therapeutic targets for the treatment of cancer. Here, the authors describe the cryo-EM structure of an antibody bound to a neoantigen complex providing insights into the specificity of the antibody.

    • Katharine M. Wright
    • , Sarah R. DiNapoli
    •  & Sandra B. Gabelli

  • Article
    | Open Access

    Genetic code expansion is limited by the degeneracy of the 61 sense codons which encode for only 20 amino acids. Here, the authors show that by combining hyperaccurate ribosomes and in vitro transcribed tRNAs, dramatic and extensive breaking of sense codon degeneracy can be achieved.

    • Clinton A. L. McFeely
    • , Bipasana Shakya
    •  & Matthew C. T. Hartman

  • Article
    | Open Access

    HLA-E is a highly conserved MHC-l recognized by NK and T cells. The authors characterize HLA-E-presented peptides recognized by CD94/NKG2x, identifying human and CMV-derived peptide ligands which can modulate NK cell activity when presented by HLA-E, including for selective NK cell activation.

    • Brooke D. Huisman
    • , Ning Guan
    •  & Michael E. Birnbaum

  • Article
    | Open Access

    Replacement of oxoamide units with thioamides in peptide therapeutics is a valuable tactic to improve biological activity and resistance to enzymatic hydrolysis. Here, the authors develop a direct coupling of readily available nitroalkane and amines with elemental sulfur and base and provide an efficient way to form thioamides and thiopeptides.

    • Xiaonan Wang
    • , Silong Xu
    •  & Jing Li

  • Article
    | Open Access

    In this work, the authors report the Cryo-EM structure of PNF-18, a biotechnologically engineered peptide fibril that enhances retroviral infectivity. The peptide fibrils mature into polymorphic amyloid structures in a time-dependent manner. The structure provides insights into the molecular basis of peptide nanofibrils as retroviral transduction enhancers.

    • Thomas Heerde
    • , Desiree Schütz
    •  & Marcus Fändrich

  • Article
    | Open Access

    The mechanism of action of the antibacterial tripeptide AMC-109 is unclear. Here, Melcrová et al. show that AMC-109 self-assembles into stable aggregates with a cationic surface, and then individual peptides insert into the bacterial membrane and disrupt membrane nanodomains, thus affecting membrane function without forming pores.

    • Adéla Melcrová
    • , Sourav Maity
    •  & Wouter H. Roos

  • Article
    | Open Access

    In this work, the authors synthetized hydrogels that mimic cryptic sites in the native extracellular matrix (ECM) using switch peptides. They report how in response to enzymes on the surface of endothelial cells the inert matrix is transformed into a bioadhesive synthetic ECM.

    • Yumeng Zhu
    • , Yulia Shmidov
    •  & John B. Matson

  • Article
    | Open Access

    Challenges rearing juvenile cone snails have limited our understanding of their developmental biology. This study cultured Conus magus cone snails and revealed how complex morphological, behavioural and molecular changes facilitate the ontogenetic shift from juvenile worm-hunters to fish-hunting adults.

    • Aymeric Rogalski
    • , S. W. A. Himaya
    •  & Richard J. Lewis

  • Article
    | Open Access

    Cyclic peptides are important bioactive compounds and drugs, synthesised by enzymatic side-chain macrocyclization of ribosomal peptides, which rarely involves histidine residues. Here, the authors report the discovery and biosynthesis of tricyclic lanthipeptide noursin, constrained by a tri amino acid labionin crosslink and histidine-to-butyrine crosslink, which is important for copper binding of noursin.

    • Yuqing Li
    • , Yeying Ma
    •  & Huan Wang

  • Article
    | Open Access

    Stings of certain ant species can cause intense, long-lasting nociception. Here, authors show that the major contributors of these symptoms are vertebrate-selective defensive venom peptides which modulate the activity of voltage-gated sodium channels.

    • Samuel D. Robinson
    • , Jennifer R. Deuis
    •  & Irina Vetter

  • Article
    | Open Access

    Engineering protein biosensors that respond to biomolecules by triggering cellular responses has largely relied on binding rigid molecules. Here, the authors develop a computational strategy for designing signaling complexes between conformationally dynamic proteins and peptides.

    • Robert E. Jefferson
    • , Aurélien Oggier
    •  & Patrick Barth

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