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This page provides an overview of the most interesting developments in the areas encompassing the fields of organic chemistry and chemical biology. This includes diverse topics, from organic synthesis, application of chemical methods for investigation of biological systems, development of functional organic materials and biomaterials to research on polymers and hydrogels.
Understanding the complex relationships between enzyme sequence, folding stability and catalytic activity is essential for applications, but current technologies cannot simultaneously resolve both stability and activity phenotypes and couple these to gene sequences at large scale. Here, the authors report Enzyme Proximity Sequencing (EP-Seq), a deep mutational scanning method to assay both expression level and catalytic activity of thousands of oxidoreductase variants from a cellular pool in a single experiment.
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.
The development of synthetic receptors capable of selectively binding monosaccharides is highly challenging. Here, authors present the efficient synthesis of these receptors based on foldamers, achieved through complexation-induced equilibrium shifting.
Environmentally adaptive hydrogels have great potential as soft robotics but achieving self-regulated reversal shape deformation in homogenous hydrogels under a constant stimulus is challenging. Here, the authors report responsive hydrogels functionalized with two photoswitchable spiropyrans that exhibit self-regulated transient deformation reversal when subjected to constant illumination.
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.
Despite the structural significance of boroxines in different classes of materials, their applicability in aqueous media is limited by their hydrolytic instability. Here, the authors discovered a water-stable boroxine structure with excellent pH stability and water-compatible dynamic covalent bonds.
The application of the LCC variant of polyethylene terephthalate (PET) hydrolase for industrial degradation of PET has been hindered by the 10% of nonbiodegradable PET. Here, the authors use a computational strategy to engineer TurboPETase which outperforms other PETase variants and achieves nearly complete depolymerization of the postconsumer PET bottles at a high, industrially relevant, level of solids loading.
It is desirable to be able to mimic the properties of skin with hydrogels, but challenging to achieve. Here, the authors report the use of functionalised extracellular vesicles as crosslinkers for skin-mimicking hydrogels with good mechanical strength.
Mycoplanecins show promising activity against tuberculosis. Here, the authors identify and study mycoplanecins’ biosynthesis, antibacterial effects, and binding mechanism to DnaN, suggesting potential for fighting multidrug-resistant tuberculosis.
Utilization of the entire lignocellulose is essential for sustainable and cost-effective biorefineries, but it is hindered by a trade-off between efficient carbohydrate utilization and lignin-to-chemical conversion yield. Here, the authors report a mild lignocellulosic fractionation process using aqueous diethylamine which produces a carbohydrate fraction susceptible to enzymatic hydrolysis and a high-quality lignin that delivers high monomer yields upon catalytic amination and depolymerization.
Near-infrared luminescence is useful for advance applications, but is challenging to achieve through clusteroluminescence. Here, the authors report the use of amine-initiated polyesters for amine-ester clusters with near-infrared emission.
Stimuli-responsive emulsions are useful for long-term storage combined with controlled release, but the fundamental mechanism behind this release is not established. Here, the authors report a study into the effect of individual microgel morphology on the destabilisation of responsive emulsions.
Molecular twist is a characteristic component of molecular machines. Here the authors report a kinetically selective synthesis of tightly- and loosely-twisted isomers of a trinuclear Pd-macrocycle and their markedly different molecular behaviours.
The synthesis of molecular knots remains challenging. Here, the authors report the synthesis of a chiral molecular trefoil metallaknot by self-assembly which contains only 54 atoms in the backbone.
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.
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.
Visible light-induced glycosylation reactions are achieved by either photoactivating a photosensitizer or using a stoichiometric activator, while glycosylation via a photoactive glycosyl donor was so far not reported. In this study, the authors develop a photosensitizer free visible-light-mediated glycosylation approach using photoactive 2-glycosyloxy tropone as the donor, obtaining a wide range of O-glycosides or oligosaccharides.
“Cycloparaphenylenes consisting of are cyclic π-conjugated structures presetting interesting physical properties upon functionalization. However, the ring strain and steric hindrance of the substituents hamper the functionalization of small sized cycloparaphenylenes. Here, the authors describe a [6]cycloparaphenylene with twelve methoxy units employed to form a rotaxane with in-plane aromaticity upon oxidation.”
Reperfusion is a main strategy for restoring blood supply after ischemic stroke, but it induces neuroinflammation that undergoes dynamic progression, hindering the treatment of ischemic stroke. Here, the authors report a pathogenesis-adaptive nanosystem for sequential and on-demand regulation of reperfusion-induced dynamic neuroinflammation for ischemic stroke therapy.
Polymers are promising for mRNA delivery, but can have limited efficacy in hard to transfect cells. Here, the authors report charge-altering releasable transporters for improved mRNA transfection in primary T-lymphocytes and enhanced and selective protein expression in vivo.
Heparan sulfate (HS) and chondroitin sulfate (CS) are different glycosaminoglycan chains that are attached to core proteins via the same linker tetrasaccharide, and it was unclear how core proteins are specifically modified with HS or CS. Here, the authors determine that the CS-initiating glycosyltransferase CSGALNACT2 is promiscuous, whereas the HS-initiating glycosyltransferase EXTL3 selects only certain core proteins for modification.
Cellular glycosylation is complex and heterogeneous, which is challenging to reproduce synthetically. Here, the authors report on enzymatic remodelling of multivalent glycosylated bacteriophages to produce genetically encoded library of N-glycans which can be used to measure glycan-protein interactions with lectins on the surface of live cells and organs.
Polymerizations in living systems can effectively regulate cell functions and behaviors, but their uses have been hindered by the existence of complicated intracorporal interferences, the needs of high concentration of monomers and extra stimulates. Here, the authors address these issues by developing a nanocompartment-confined strategy to achieve broad-spectrum polymerizations in living systems.
Live-cell RNA imaging with high spatial and temporal resolution remains a major challenge. Here the authors design spirocyclic rhodamine probes that enable a fluorescent light-up aptamer system suitable for visualizing RNAs in live or fixed cells with two different super-resolution microscopy modalities SMLM and STED.
Bioprinting has potential in the biofabrication of three dimensional tissues, but is poorly suited to the manipulation of neural organoids. Here, the authors develop a bioprinting platform to allow the arrangement of organoids to form assembloids.
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.
Integration of nanomaterials and enzymes has potential in the development of robust biocatalysts, but preparation can still be technically challenging. Here, the authors report the preparation of a hydrogen-bonded organic framework biocatalyst and its use as an immunosensor.
Ketone α-alkylation at the more hindered site is challenging. Here, the authors report a highly regioselective nickel-catalysed allylic alkylation of unsymmetrical ketones at the more-hindered α-site with allylic alcohols.
Efficient valorization of lignin, a sustainable source of functionalized aromatic products, would reduce dependence on fossil-derived feedstocks. Here, the authors directly transform lignin into valuable functionalized diaryl ethers in near-theoretical-maximum yields, using oxidative cross coupling under copper catalysis.
Enantioselective α-allylic allenylation of carbonyls is a straightforward approach to access chiral allenes that are of significant relevance as synthons and bio-active products. Here, the Luo group describe an asymmetric α-allylic allenylation of β-ketocarbonyls and aldehydes with 1,3-enynes, via a combined chiral primary amine and palladium catalyst system.
Metal-catalysed oxidation of proteins varies in selectivity and depends on the surface residues to direct the reaction. Here, the authors use polyoxometalate clusters as inorganic ligands for Cu ions, enabling the regioselective oxidative cleavage of a protein via reactive oxygen species in the vicinity of its binding sites.
RiPP discovery has expanded the scope of post-translational modification chemistry, but genome mining of RiPP classes remains an unsolved challenge. Here, the authors employed bioinformatics and synthetic biology approaches to discover and characterize an unknown class of RiPPs, defined by an unusual amino-modified C-terminus.
Bio-degradation of poly(butylene adipate-co-terephthalate) is an attractive tactic but requires an effective hydrolytic enzyme. Here, the authors demonstrate that cutinases are highly potent PBAT-decomposing enzymes and their mechanism is proposed based on substrate-binding mode.
The development of direct-acting antivirals to combat COVID-19 remains an important goal. Here the authors design covalent inhibitors that target the papain-like protease from SARS-CoV-2. The most promising inhibitor blocks viral replication in mammalian cells.
The difunctionalization of diazo compounds, traditionally with one nucleophile and one electrophile, is a powerful strategy. Here, the authors develop a path of electrochemical oxidative difunctionalization of diazo compounds with two different nucleophiles.
Biosynthesis of complex polyketides by polyketide synthases often relies on trans-acting enzymes to modify the intermediates. Here, the authors elucidate how β-methylation enzymes identify their substrates. The recognition is imperfect, resulting in a doubly β-methylated virginiamycin derivative.
Terpene cyclases enable the synthesis of (poly)cyclic carbon frameworks via ring closure of linear polyenes. Here, the authors report in-situ formed fluorinated-alcohol-amine supramolecular clusters that mimic terpene cyclases for shape-controlled polyene cyclizations.
MraY is a membrane enzyme required for bacterial cell wall synthesis. Here, the authors modify sphaerimicins as antibacterials targeting it via structure-based design and synthesis through two key reactions, showing a platform for further development of MraY inhibitors as antibacterials.
Converting low-cost inorganic chemicals into value-added organic chemicals is a longstanding goal in chemistry. Here the authors describe a silver-catalysed chemoselective carbene N−H insertion reaction, providing access to primary amines from aqueous ammonia and diazo compounds.
Syntheses of quinine have fascinated organic chemists for over a hundred years. Here, the authors developed an organocatalyst-mediated pot-economical enantioselective total synthesis using five reaction vessels.
Boronic acids are useful reagents in organic synthesis and thus methods to prepare these compounds under mild conditions are desirable. Here, the authors synthesize boronic acids via photocatalytic decarboxylation of benzoic acids followed by borylation; guanidine-type additives are used to assist the process.
Methods that enable the cleavage of Si−C(sp3) bonds catalytically remain rare. Here the authors report the synthesis of spirosilacycles via palladium-catalysed spiro-sila-cyclization of trialkylsilane derivatives; the reaction proceeds via cleavage of a C(sp3)−Si bond and insertion of an alkylpalladium complex.
The interception of one chemical intermediate with another intermediate is very challenging, as intermediates may be incompatible or too reactive, but could result in a streamlined method of organic synthesis. Here, the authors demonstrate enantioselective four-component reactions via the coupling of two intermediates.
The modification of peptides and proteins for application in drug discovery and chemical biology is currently a rapidly growing field of research. Here, the authors report a photocatalytic diselenide contraction method for the dimerization and site-specific functionalisation of peptides and protein.
The occurrence of isomers of the bicyclic octapeptide α-amanitin, which presents a macrolactam with a tryptathionine cross-link forming a handle, has been reported under the term of atropoisomers. Here, the authors synthesize its analogs and analyse their isomers, proposing and describing for them the term ansamer.
Catalysed oxidative C-C bond formation reactions are important in the synthesis of natural products, but poorly tolerated by polyphenolic flavones. Here the authors report the reactivity of molecular oxygen in alkaline water without added catalyst for the synthesis of a collection of flavone dimers and trimers.
The development of photochromic systems is an important and growing area of research, in particular for bioactive molecular photoswitches. Here, the authors report on photopharmacological antimitotic agents, operational under visible light, based on a peptide-derived hemipiperazine photochrome.
Ribosomally synthesized and post-translationally modified peptides are a source of antimicrobials. Here, the authors report a platform for the rapid evaluation and characterization of biosynthetic gene clusters that enables the identification of 30 structurally diverse modified peptides, including three showing antimicrobial activities.
Controlling the enantioselectivity of radical reactions is a persistent challenge in organic synthesis. Here, the authors report a method to form asymmetric pyridine derivatives via the combination of chiral palladium catalysis and electrochemistry.
Efficient engineering of enzymes for expanded substrate scope is currently challenging. Here, the authors develop simple principles of how to design and interpret Substrate Multiplexed Screening assays to guide protein engineering to enable activity improvements with simultaneously with multiple substrates.