N ‐Functionalised Imidazoles as Stabilisers for Metal Nanoparticles in Catalysis and Anion Binding

Metal nanoparticles (NPs) have physicochemical properties which are distinct from both the bulk and molecular metal species, and provide opportunities in fields such as catalysis and sensing. NPs typically require protection of their surface to impede aggregation, but these coatings can also block access to the surface which would be required to take advantage of their unusual properties. Here, we show that alkyl imidazoles can stabilise Pd, Pt, Au, and Ag NPs, and delineate the limits of their synthesis. These ligands provide an intermediate level of surface protection, for which we demonstrate proof‐of‐principle in catalysis and anion binding

The helix-hairpin-helix DNA-binding motif: A structural basis for non-sequence-specific recognition of DNA

One, two or four copies of the 'helix-hairpin-helix' (HhH) DNA-binding motif are predicted to occur in 14 homologous families of proteins. The predicted DNA-binding function of this motif is shown to be consistent with the crystallographic structure of rat polymerase ß, complexed with DNA template-primer and with biochemical data. Five crystal structures of predicted HhH motifs are currently known: two from rat pol ß and one each in endonuclease III, AlkA and the 5' nuclease domain of Taq pol I. These motifs are more structurally similar to each other than to any other structure in current databases, including helix-turn-helix motifs. The clustering of the five HhH structures separately from other bi-helical structures in searches indicates that all members of the 14 families of proteins described herein possess similar HhH structures. By analogy with the rat pol ß structure, it is suggested that each of these HhH motifs bind DNA in a non-sequence-specific manner, via the formation of hydrogen bonds between protein backbone nitrogens and DNA phosphate groups. This type of interaction contrasts with the sequence-specific interactions of other motifs, including helix-turn-helix structures. Additional evidence is provided that alphaherpesvirus virion host shutoff proteins are members of the polymerase I 5'-nuclease and FEN1-like endonuclease gene family, and that a novel HhH-containing DNA-binding domain occurs in the kinesin-like molecule nod, and in other proteins such as cnjB, emb-5 and SPT6

High-definition polyphosphoesters: between nucleic acids and plastics

Polyphosphoesters are common to both genetics and cutting-edge polymer science. This review seeks to reframe current conceptions of the boundaries of nucleic acid and polymer chemistry, showing that vital ‘stepping stones’ are now in place, allowing us to make a journey through chemical space between DNA and the synthetic polyphosphoesters. These liminal classes of macromolecule address vital questions about sequence control in polymers, single polymer chain folding, programmed self-assembly, nanoscale photophysics, and chemical data storage. In taking this path, we will impinge upon biochemistry, medicine, photophysics, supramolecular chemistry, nanotechnology, information technology and materials science. The synthetic methods we already have in hand have only just begun to show their promise in all these fields

Nanotechnology and Biotechnology: Two Way Traffic

Editorial overview for special issue of Current Opinion in Biotechnology on Nanobiotechnolog

Degradable Polymers and Nanoparticles Built from Salicylic Acid

As more evidence emerges supporting the possibility that non-steroidal anti-inflammatory drugs, especially aspirin (acetyl salicylic acid), might have a role in the prevention and management in certain types of cancer, there have been several attempts to fabricate salicylic acid-based polymers that can be employed in the targeted therapy of tumours. The primary disadvantage so far has been in use of non-therapeutic polymeric backbones that constitute the majority of the therapeutic particle’s size. The focus of this research is the creation of a biodegradable polymer consisting only of salicylic acid, and its use as the main building block in targeted nanotherapeutics that would consequently provide both high local dose and sustained release of the active moiety. In this work, we demonstrate the synthesis and degradation of polysalicylates, and modulation of their size and hydrolytic stability through formation of nanostructures

Quantification of amyloid fibril polymorphism by nano-morphometry reveals the individuality of filament assembly

Amyloid fibrils are highly polymorphic structures formed by many different proteins. They provide biological function but also abnormally accumulate in numerous human diseases. The physicochemical principles of amyloid polymorphism are not understood due to lack of structural insights at the single-fibril level. To identify and classify different fibril polymorphs and to quantify the level of heterogeneity is essential to decipher the precise links between amyloid structures and their functional and disease associated properties such as toxicity, strains, propagation and spreading. Employing gentle, force-distance curve-based AFM, we produce detailed images, from which the 3D reconstruction of individual filaments in heterogeneous amyloid samples is achieved. Distinctive fibril polymorphs are then classified by hierarchical clustering, and sample heterogeneity is objectively quantified. These data demonstrate the polymorphic nature of fibril populations, provide important information regarding the energy landscape of amyloid self-assembly, and offer quantitative insights into the structural basis of polymorphism in amyloid populations

Controlled Release of Ibuprofen from Polymeric Nanoparticles

Smart polymeric systems are required that are able to release a therapeutic drug with controlled delivery. Herein we investigated the pH triggered release of ibuprofen from a polymeric nanoparticle system prepared using ring-opening metathesis polymerisation. The co-polymerisation of ibuprofen and poly(ethylene)glycol monomers followed by self-assembly produced a nanoparticle system that was shown to be stable at neutral pH but releases ibuprofen in alkaline condition

Selection of optimised ligands by fluorescence-activated bead sorting

The chemistry of aptamers is largely limited to natural nucleotides, and although modifications of nucleic acids can enhance target aptamer affinity, there has not yet been a technology for selecting the right modifications in the right locations out of the vast number of possibilities, because enzymatic amplification does not transmit sequence-specific modification information. Here we show the first method for the selection of specific nucleoside modifications that increase aptamer binding efficacy, using the oncoprotein EGFR as a model target. Using fluorescence-activated bead sorting (FABS), we have successfully selected optimized aptamers from a library of >65 000 variations. Hits were identified by tandem mass spectrometry and validated by using an EGFR binding assay and computational docking studies. Our results provide proof of concept for this novel strategy for the selection of chemically optimised aptamers and offer a new method for rapidly synthesising and screening large aptamer libraries to accelerate diagnostic and drug discovery

Architecture-controlled release of ibuprofen from polymeric nanoparticles

Smart polymeric systems are required that are able to release a therapeutic drug with control over timing and location of delivery. Herein we have investigated the architecture-controlled and pH-triggered release of ibuprofen from a polymeric nanoparticle system prepared using ring-opening metathesis polymerisation. The co-polymerisation of norbornene-derived ibuprofen (NB-Ibu) and poly(ethylene glycol) (NB-PEG) monomers produced polymers with block and random sequence architectures. Self-assembly into nanoparticle systems and release of ibuprofen only under basic conditions was shown to be controlled by polymer sequence