Biological techniques articles within Nature Chemistry

Featured

  • Article |

    High-throughput proteome-wide methods for identifying endogenous proteins that phase separate or partition into condensates during certain physiological events are needed but remain a challenge. Now, a high-throughput, unbiased and quantitative strategy can identify endogenous biomolecular condensates and screen proteins involved in phase separation on a proteome-wide scale.

    • Pengjie Li
    • , Peng Chen
    •  & Yiwei Li

  • Article |

    Lipidomics aims to uncover lipid functions in biological systems and disease. Quantifying lipids is challenging due to highly diverse chemical structures. Here a diazobutanone-assisted isobaric labelling method is developed that relies on diazobutanone and isobaric mass tags to target phosphate- and sulfate-containing lipids, enabling multiplexed lipidomic quantification in complex mixtures.

    • Ting-Jia Gu
    • , Peng-Kai Liu
    •  & Lingjun Li

  • Article |

    Detecting genetic mutations, such as single nucleotide polymorphisms (SNPs), is essential for disease diagnostics but can be difficult using homomultivalent DNA hybridization-based approaches. Now, heteromultivalent hybridization is used to fine-tune binding specificity for the detection of one or two SNPs in a single target, enabling straightforward discrimination between adjacent and distant mutations and different viral strains.

    • Brendan R. Deal
    • , Rong Ma
    •  & Khalid Salaita

  • Article |

    Generating aptamers for use as affinity reagents in analytical applications is important, but SELEX, the standard method for aptamer generation, is unable to select for pre-defined binding affinities. Now, by combining efficient particle display, high-performance microfluidic sorting and high-content bioinformatics, the method ‘Pro-SELEX’ can afford the quantitative generation of aptamers with programmable binding affinities.

    • Dingran Chang
    • , Zongjie Wang
    •  & Shana O. Kelley

  • Perspective |

    Bioresponsive hyperpolarized probes contain magnetic resonance signals that can be many orders of magnitude larger than those of common, thermally polarized probes. This Perspective discusses how bioresponsive hyperpolarized probes can be directly linked to biological events to give functional information, enabling the mapping of physiological processes and diseases in real time using magnetic resonance.

    • Goran Angelovski
    • , Ben J. Tickner
    •  & Gaoji Wang

  • News & Views |

    Constructing aptamers with desired target-binding affinities may lead to new applications but is challenging. Now, a new method using a high-dimensional microfluidic approach enables quantitative isolation of aptamers with programable binding affinities.

    • Ping Song
    •  & Chunhai Fan

  • In Your Element |

    Organisms that glow are perhaps eerie. Vadim Viviani ponders on the luciferin–luciferase systems responsible for their intriguing bioluminescence.

    • Vadim R. Viviani

  • Article |

    Techniques to specifically modulate protein activity are needed to interrogate spatial effects in cellular processes. A genetically encoded method for site-specific protein–protein conjugation based on a photoclick chemical reaction has now been developed. This method permits rapid and irreversible reassembly of bioactive proteins from non-functional split fragment pairs with full spatiotemporal control in solution, biomaterials and living mammalian cells.

    • Emily R. Ruskowitz
    • , Brizzia G. Munoz-Robles
    •  & Cole A. DeForest

  • In Your Element |

    Jane Liao and Allie C. Obermeyer explore the discovery, modification and applications of green fluorescent protein, best known for its use as a tool to cast light on cellular processes.

    • Jane Liao
    •  & Allie C. Obermeyer

  • Article |

    A nanopore framework has been developed to reveal the crosstalk effect on the renin–angiotensin system. By reading the single-amino-acid differences in angiotensin peptides with high accuracy and high efficiency, the selective inhibition of angiotensin-converting enzyme by angiotensin-converting enzyme 2 was revealed. This activity was shown to be suppressed by the spike protein of SARS-CoV-2.

    • Jie Jiang
    • , Meng-Yin Li
    •  & Yi-Tao Long

  • Article |

    Identifying and quantifying the biodistribution of synthetic polymeric nanoparticles in biological milieu is crucial for biomedical applications. Now, it has been shown that encoded polymeric amphiphiles with discrete molar masses undergo sequence- and length-dependent self-assembly into precise digital micelles that can be used in direct sequence reading and ex vivo label-free quantification assays.

    • Qiangqiang Shi
    • , Hao Yin
    •  & Shiyong Liu

  • Article |

    A method has been developed to identify RNA transcript isoforms at the single-molecule level using solid-state nanopore microscopy. In this method, target RNA is refolded into RNA identifiers with designed sets of complementary DNA strands. Each reshaped molecule carries a unique sequence of structural (pseudo)colours that enables identification and quantification using solid-state nanopore microscopy.

    • Filip Bošković
    •  & Ulrich Felix Keyser

  • Article |

    Oligonucleotide catalysts such as ribozymes and DNAzymes can cleave RNA efficiently and specifically but are typically dependent on high concentrations of divalent cations, limiting their biological applications. A modular XNAzyme catalyst composed of 2′-deoxy-2′-fluoro-β-d-arabino nucleic acid (FANA) has now been developed that can cleave long (>5 kb), highly structured mRNAs under physiological conditions and enables allele-specific catalytic RNA knockdown inside cells.

    • Alexander I. Taylor
    • , Christopher J. K. Wan
    •  & Philipp Holliger

  • Article
    | Open Access

    The design of photoactivatable fluorophores—which are required for some super-resolution fluorescence microscopy methods—usually relies on light-sensitive protecting groups imparting lipophilicity and generating reactive by-products. Now, it has been shown that by exploiting a unique intramolecular photocyclization, bright and highly photostable fluorophores can be rapidly generated in situ from appropriately substituted 1-alkenyl-3,6-diaminoxanthone precursors.

    • Richard Lincoln
    • , Mariano L. Bossi
    •  & Stefan W. Hell

  • News & Views |

    Extending mass spectrometry measurements of biomolecules into the megadalton regime is challenging due to the limited resolving power of currently used mass analysers. Now, using single ion-charge detection Orbitrap mass spectrometry, a mass accuracy of 0.001% has been demonstrated for protein particles larger than 9 MDa.

    • Muhammad A. Zenaidee
    •  & Joseph A. Loo

  • In Your Element |

    Christine M. Le takes a look at 2-[18F]fluoro-2-deoxyglucose and explains how this radioactive sugar could help to save your life.

    • Christine M. Le

  • Article
    | Open Access

    The mass precision and resolution in charge-detection mass spectrometry can be improved by correcting frequency drifts of single ions. Now, chasing these individual ions for seconds in an Orbitrap mass spectrometer has revealed the exceptional stability of ultra-high-mass ions, culminating in an effective resolution of greater than 100,000 at m/z = 35,000.

    • Tobias P. Wörner
    • , Konstantin Aizikov
    •  & Albert J. R. Heck

  • Article |

    A photoredox-mediated SNAr reaction has now been developed for the direct radiofluorination of unactivated aryl halides. A series of arenes can be radiofluorinated in a site-selective manner from readily available aryl halide precursors under mild conditions. This strategy allows efficient 19F/18F isotopic exchange, enabling rapid PET probe diversification and clinical tracer preparation.

    • Wei Chen
    • , Hui Wang
    •  & Zibo Li

  • Article |

    An integrated multiprotein nanopore has been fabricated using components from all three domains of life. This molecular machine opens the door to two approaches in single-molecule protein analysis, in which selected substrate proteins are unfolded, fed to into the proteasomal chamber and then processed either as fragmented peptides or intact polypeptides.

    • Shengli Zhang
    • , Gang Huang
    •  & Giovanni Maglia

  • Article |

    Imaging-based companion diagnostics can provide real-time information to match therapies to patients; however, glutathione is abundant in most cells, making it an unlikely candidate for companion diagnosis. Now, a chemical probe has been developed that can detect elevated glutathione concentrations via photoacoustic imaging. Using this probe enables normal and pathological states in a lung cancer model to be distinguished.

    • Melissa Y. Lucero
    •  & Jefferson Chan

  • Article |

    Zinc fluxes have now been shown to be essential in the fertilization of amphibian eggs. Furthermore, manganese(ii), which is initially bound to low-molecular-weight carboxylates, is stored and released with zinc from cortical vesicles following fertilization. This rapid metal ion release blocks the otherwise fatal entry of a second sperm.

    • John F. Seeler
    • , Ajay Sharma
    •  & Thomas V. O’Halloran

  • News & Views |

    The continuous monitoring of proteins is a current challenge in medical diagnostics. A new electrochemical approach aiming to address this has been described. The method uses antibodies as a recognition element to achieve the real-time measurement of proteins in saliva in the mouth.

    • Kevin J. Cash
    •  & Kevin W. Plaxco

  • Article |

    A method to label membrane proteins with a DNA tag has been developed that enables the selection of DNA-encoded chemical libraries against endogenous membrane proteins on live cells. As a demonstration, a 30-million-compound DNA-encoded chemical library is screened against folate receptor, carbonic anhydrase 12 and epidermal growth factor receptor on live cells.

    • Yiran Huang
    • , Ling Meng
    •  & Xiaoyu Li

  • Article |

    Bacteria use thioester-bond-containing proteins to covalently bind to host surfaces and withstand large mechanical shocks. Now, thioester bond reactivity has been shown to be force-dependent: forces >35 pN inhibit bond cleavage by primary amine ligands, whereas forces <6 pN enable reversible reformation. This force-modulated thioester bond reactivity could potentially enable bacterial mobility and a route by which they optimize infection.

    • Alvaro Alonso-Caballero
    • , Daniel J. Echelman
    •  & Julio M. Fernandez

  • Review Article |

    Metabolic labelling with unnatural sugars can be used to selectively label tumours with chemical tags. These tags then enable the targeted delivery of molecular cargo including diagnostic and therapeutic agents. This Review Article discusses progress in the design and delivery of unnatural sugars for metabolic labelling of tumour cells and the subsequent development of tumour-targeted chemistry.

    • Hua Wang
    •  & David J. Mooney

  • Article |

    Conducting high-resolution, multiplexed imaging in living mammals is challenging because of considerable scattering and autofluorescence in tissue at visible and near-infrared wavelengths. Now, real-time, non-invasive multicolour imaging experiments in live animals have been achieved through the design of optical contrast agents for the shortwave infrared (SWIR, 1,000–2,000 nm) region and the introduction of excitation multiplexing with single-channel SWIR detection.

    • Emily D. Cosco
    • , Anthony L. Spearman
    •  & Ellen M. Sletten

  • Article |

    The biosynthesis of goadvionins—hybrid lipopeptide antibiotics—is not fully understood. An unusual acyltransferase, GdvG, has now been identified and shown to catalyse a condensation reaction between an acyl-carrier-protein-tethered very-long-chain fatty acid and an eight-residue ribosomally synthesized and post-translationally modified peptide. The position of functional groups in the very-long acyl chain have been determined by tandem mass spectrometry.

    • Ryosuke Kozakai
    • , Takuto Ono
    •  & Hiroyasu Onaka

  • Article |

    Many bacterial pathogens release effector enzymes belonging to the large Fic family, which modify host targets with nucleotide monophosphates. Now, recombinantly produced Fic enzymes have been equipped with synthetic thiol-reactive nucleotide derivatives to make covalent binary probes. The reaction of modified Fic enzymes with their targets permits covalent substrate capture and the structural determination of low-affinity ternary enzyme–nucleotide–substrate complexes.

    • Burak Gulen
    • , Marie Rosselin
    •  & Aymelt Itzen

  • News & Views |

    Identifying chromatin modifications and their interactomes is imperative to understand how chromatin functions and is regulated. Now, two new studies report on chemical tools that enable characterization of the biological interactions within native chromatin.

    • Yi Zhang
    •  & Tatiana G. Kutateladze

  • Article |

    A programmable polymer library that responds to external and internal stimuli has been developed and used to fabricate a series of nanocarriers for drug release. The carriers respond to disease biomarkers, triggering self-immolative motifs and leading to the site-specific release of therapeutics both in vitro and in vivo.

    • Penghui Zhang
    • , Di Gao
    •  & Weihong Tan

  • Article |

    It is difficult to develop suitable fluorescent probes for live-cell nanoscopy, but a general strategy is now reported that can transform regular fluorophores into fluorogenic probes with excellent cell permeability and low unspecific background signals. Using this approach, probes in a variety of colours were developed for different cellular targets and used for wash-free, multicolour, live-cell confocal and STED microscopy.

    • Lu Wang
    • , Mai Tran
    •  & Kai Johnsson

  • Article |

    Gene-circuit-based sensors have, to date, largely relied on optical proteins (such as green fluorescent protein) to report the output, which limits the signalling bandwidth. Now, an electrochemical output has been developed and integrated with cell-free gene circuits. This approach enables multiplexing of sensors and introduces the possibility of electronic-based logic, memory and response elements to synthetic biology.

    • Peivand Sadat Mousavi
    • , Sarah J. Smith
    •  & Keith Pardee

  • News & Views |

    The in situ, nanoscale positioning of a single molecule below the diffraction limit remains a challenge for chemists. Now, two approaches show how this can be accomplished through a combination of super-resolution microscopy and photo-inducible crosslinking chemistry.

    • Limin Xiang
    •  & Ke Xu

  • Article |

    Super-resolution microscopy has enabled optical imaging of individual biomolecules on the nanometre scale. Now, a new method has been developed that allows active manipulation of single-molecule targets on visualization in a sequential manner. This method, called ‘Action-PAINT’, combines real-time super-resolution microscopy (DNA-PAINT) and photoinducible crosslinking chemistry to deliver a single-molecule cargo with <30 nm selectivity.

    • Ninning Liu
    • , Mingjie Dai
    •  & Peng Yin

  • Article |

    Symmetrical protein oligomers perform key structural and catalytic functions in nature, but engineering such oligomers synthetically is challenging. Now, oppositely supercharged synthetic variants of normally monomeric proteins have been shown to assemble via specific, introduced electrostatic contacts into symmetrical, highly well-defined oligomers.

    • Anna J. Simon
    • , Yi Zhou
    •  & Andrew D. Ellington

  • Article |

    Lipid membranes—which separate cells and organelles from their environment—experience tension during various cell processes; however, measuring membrane tension is notoriously difficult. Now, a new fluorescent, mechanosensitive membrane probe called FliptR has been developed. FliptR enables simple, direct membrane tension measurements in cellular and artificial membranes.

    • Adai Colom
    • , Emmanuel Derivery
    •  & Aurélien Roux

  • News & Views |

    Enzymes can perform various biological functions because of their delicately and precisely organized structures. Now, simple inorganic nanoparticles with a rationally designed recognition capability can mimic restriction enzymes and selectively cut specific DNA sequences.

    • Aleksandar P. Ivanov
    •  & Joshua B. Edel

  • Article |

    Genome editing relies on engineered nucleases to change an organism’s DNA, but has not yet been achieved using abiotic materials. Now, chiral cysteine-capped CdTe nanoparticles are found to specifically recognize and, following photoirradiation, cut between bases T and A at the GATATC restriction site in DNA with over 90 base pairs.

    • Maozhong Sun
    • , Liguang Xu
    •  & Hua Kuang

  • Article |

    Pyrrolysyl-tRNA synthetase(PylRS)/PyltRNACUA pairs that lack the N-terminal domain but are active and orthogonal are discovered, and pairs that are mutually orthogonal to existing PylRS/PyltRNACUA pairs are developed. Mutually orthogonal PylRS/PyltRNA pairs are combined to genetically encode the incorporation of distinct ncAAs into proteins synthesized in E. coli.

    • Julian C. W. Willis
    •  & Jason W. Chin

  • Article |

    I-motif DNA structures are thought to form in cytosine-rich regions of the genome and to have regulatory functions; however, in vivo evidence for the existence of such structures has so far remained elusive. Now an engineered antibody that is selective for i-motif structures has been developed and used to detect i-motifs in the nuclei of human cells.

    • Mahdi Zeraati
    • , David B. Langley
    •  & Daniel Christ

  • Article |

    Cell-to-cell variation in gene expression creates a need for techniques that characterize expression at the level of individual cells. Now, a technique for characterizing mRNA expression has been developed. The technique uses the intracellular self-assembly of magnetic nanoparticles to quantitate RNA levels at the single-cell level.

    • Mahmoud Labib
    • , Reza M. Mohamadi
    •  & Shana O. Kelley

  • News & Views |

    Rational engineering of biosynthetic assembly lines for production of new compounds is an attractive prospect, yet it presents many challenges. Learning from biology, some of the rules for expanding the chemical diversity of non-ribosomal peptides have been uncovered in two recent studies.

    • Binuraj R. K. Menon
    •  & Matthew Jenner

  • News & Views |

    Mass spectrometry is a powerful technique for analysing proteins, yet linking higher-order protein structure to amino acid sequence and post-translational modifications is far from simple. Now, a native top-down method has been developed that can provide information on higher-order protein structure and different proteoforms at the same time.

    • Kathrin Breuker

  • Article |

    Biomaterials that respond to precise combinations of environmental cues represent an important technology for tissue engineering and next-generation drug delivery systems. Now, a modular framework to programme material degradation following Boolean logic has been demonstrated by specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within hydrogel cross-linkers.

    • Barry A. Badeau
    • , Michael P. Comerford
    •  & Cole A. DeForest

  • Article |

    An integrated native mass spectrometry and top-down proteomics method using Fourier transform ion cyclotron resonance has been developed for the characterization of macromolecular protein complexes. This approach directly yields primary to quaternary structural information in a single native top-down experiment.

    • Huilin Li
    • , Hong Hanh Nguyen
    •  & Joseph A. Loo

  • Article |

    Modular hybridization probes (M-Probes) have been developed that enable sequence-selective binding of complex nucleic acid targets. The M-probes can target sequences that: are hypervariable at prescribed loci, are long continuous sequences of over 500 nucleotides, or contain repetitive sequences. A hybrid-capture assay using the M-probes was developed that was capable of determining the exact triplet repeat expansion number in the Huntington's gene from genomic DNA.

    • Juexiao Sherry Wang
    • , Yan Helen Yan
    •  & David Yu Zhang

  • News & Views |

    Biomimetic molecules that can be easily tailored offer numerous opportunities. Now, boron-based clusters have been shown to be excellent biomimetics. The ease with which the cluster surfaces can be modified stands to change how chemists might go about preparing materials for imaging, drug delivery and other applications.

    • Marek B. Majewski
    • , Ashlee J. Howarth
    •  & Omar K. Farha

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