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The mechanism by which RNA and proteins form liquid organelles is not fully understood, but William Aumiller Jr and Christine Keating have now demonstrated that charge-mediated phase separation can generate droplets that resemble a simple model of these assemblies. By controlling the phosphorylation of cationic peptides using a kinase/phosphatase enzyme pair, Aumiller and Keating were able to reversibly form and dissolve liquid droplets from the peptides and RNA. The cover image depicts the formation of liquid organelles of different sizes.Article p129IMAGE: CHRISTINE KEATING AND WILLIAM AUMILLER JRCOVER DESIGN: KAREN MOORE
The modification of proteins with fluorophores, drugs and polymers is required for many applications, yet conjugation reactions often generate a heterogeneous mixture of products. A collection of articles in this issue focuses on methods to modify proteins in a site-selective manner.
Mass production at the nanoscale requires molecular machines that can control, with high fidelity, the spatial orientation of other reactive species. The demonstration of a synthetic system in which a molecular robotic arm can be used to manipulate the position of a chemical cargo is a significant step towards achieving this goal.
The reactivity of glycosyl donors is often explained by invoking putative glycosyl cation intermediates but, until now, they have not been observed in the condensed phase.
The discovery of a tetrapeptide containing a reactive cysteine provides a method to site-selectively modify peptides and proteins, even if other cysteine residues are present in the polypeptide chain.
A wide range of different aqueous chemistries for the site-selective modification of proteins have been described over the past decade. This Perspective discusses the scope and potential of chemical site-selective protein-modification methods in the context of their biological and therapeutic applications.
Antibody–drug conjugates have shown considerable promise for treating disease. However, in order to deliver their full potential, sophisticated site-specific conjugation technologies are needed. This Perspective provides an overview of the different methods used for the site-specific attachment of cytotoxic agents to antibodies.
Incorporation of a π-clamp—a four-residue sequence (Phe-Cys-Pro-Phe)—into a protein enables the site-specific modification of the π-clamp cysteine side-chain. The π-clamp can be genetically encoded and does not require protecting-groups or catalysts to provide selective conjugation.
Intracellular bodies called liquid organelles are rich in nucleic acids and proteins, and are thought to occur by liquid–liquid phase coexistence. Now, enzymatic control over the phosphorylation state of a simple cationic peptide, thereby altering its electrostatic interaction with RNA, has been shown to drive formation and dissolution of droplets that mimic these intracellular liquid bodies.
Factory assembly lines often feature robots that pick up, reposition and connect components in a programmed manner. Now, it has been shown that a molecular machine is able to pick up a cargo, reposition it, set it down and release it at a site approximately 2 nm away from the starting position.
Single operation transformations that enantioselectively install a stereogenic centre while introducing a distal functional group are synthetically valuable but rare processes. Now, a copper-catalysed reductive relay hydroamination process that simultaneously creates a remote chiral centre is described. The resulting γ- and δ-chiral amines are important structural elements in many pharmaceutical agents and natural products.
Little is known about how the identity of a leaving group affects the dynamics of a bimolecular nucleophilic substitution reaction. A study of the reaction of F− with CH3Cl, and comparison to its reaction with CH3I, now reveals key insights into such effects, with reactant orientation considered a key factor in understanding the behaviour observed.
The selective conversion of abundant and inexpensive alkane feedstocks into value-added speciality chemicals is a significant and challenging goal, and methods for catalytically converting alkanes into useful linear alkylsilanes are unknown, to date. Now, a strategy combining alkane dehydrogenation with regioselective olefin isomerization–hydrosilylation to produce linear alkylsilanes is described.
DNA nanostructures are typically used as molecular scaffolds. Now, it has been shown that they can also act as reusable templates for ‘molecular printing’ of DNA strands onto gold nanoparticles. The products inherit the recognition elements of the parent template: number, orientation and sequence asymmetry of DNA strands. This converts isotropic nanoparticles into complex building blocks.
Doping mesoporous materials is an attractive way to tune their properties, but typically disrupts the host materials’ structures. Ultrasmall graphitic pencil nanodots have now been prepared, doped with heteroatoms, and inserted in a well-dispersed manner within the ordered structure of mesoporous materials including TiO2, carbon and silica, by a co-assembly approach.
The encapsulation and stabilization of an oxygen tolerant [NiFe]-hydrogenase, sequestered within the bacteriophage P22 capsid, has now been achieved through a directed self-assembly process. Probing the catalytic activity and infrared spectroscopic signatures of the bio-inspired assembly shows that the capsid provides stability and protection to the hydrogenase cargo.
Glycosyl cations are universally accepted as key intermediates in the mechanism of glycosylation—the reaction that covalently links carbohydrates to other molecules—but their high reactivity makes them difficult to characterize. Using HF/SbF5 superacid, two glucosyl cations have been generated and stabilized, then characterized by NMR spectroscopy aided by computation and their conformation elucidated.