Exonic splicing enhancer (ESE) sequences are bound by serine & arginine-rich (SR) proteins, which in turn enhance the recruitment of splicing factors. It was inferred from measurements of splicing around twenty years ago that Drosophila doublesex ESEs are bound stably by SR proteins, and that the bound proteins interact directly but with low probability with their targets. However, it has not been possible with conventional methods to demonstrate whether mammalian ESEs behave likewise. Using single molecule multi-colour colocalization methods to study SRSF1-dependent ESEs, we have found that that the proportion of RNA molecules bound by SRSF1 increases with the number of ESE repeats, but only a single molecule of SRSF1 is bound. We conclude that initial interactions between SRSF1 and an ESE are weak and transient, and that these limit the activity of a mammalian ESE. We tested whether the activation step involves the propagation of proteins along the RNA or direct interactions with 3′ splice site components by inserting hexaethylene glycol or abasic RNA between the ESE and the target 3′ splice site. These insertions did not block activation, and we conclude that the activation step involves direct interactions. These results support a model in which regulatory proteins bind transiently and in dynamic competition, with the result that each ESE in an exon contributes independently to the probability that an activator protein is bound and in close proximity to a splice site.

The synthetic P-Z genetic system base pairs by a unique arrangement of three hydrogen bonds. Burley and colleagues describe a study that highlights how loss of this synthetic genetic information is driven by Z mispairing with G. They show that G-Z mispairing has two highly pH-dependent pairing regimes whereby Z acts as an anionic mimic of C in a G-C base pair at pH > 7.8.

The synthesis of a series of platinum complexes containing cyclooctadiene ligands with the general structure PtMeL(R-cod) (where L = Cl, I, nC 3 F 7 , iC 3 F 7 , nC 8 F 17 , Me, aryl, alkynyl and R = H, Me, Et, iPr, nBu, iBu, nHex, Ph) is presented. All complexes are remarkably stable and were obtained in excellent yields. Their structure in both solution and the solid state were explored by crystal structures and multinuclear ( 1 H, 13 C, 19 F, 195 Pt) NMR spectroscopy. Cytotoxicity experiments with selected complexes in HeLa cells revealed higher toxicity in comparison to that of cisplatin for most of the structures.

Investigations on the metal-organic (MO)CVD of platinum nanoparticles on spherical, chemical vapor synthesis (CVS)produced SiO 2 substrates are discussed in this paper. Commercially available methylcyclopentadienyl trimethyl platinum (MeCpPtMe 3 ) (1) and three newly synthesized cyclooctadienyl platinum precursors are chosen and tested during a continuous CVD/CVS process. The synthesis of this new class of stable, halogen-free precursors for atmospheric pressure (AP)CVD is presented. The complexes [PtMe 2 (R-COD)], where R ¼ Et (2a), n Bu (2b), and i Bu (2c), are shown to be highly suitable for the preparation of platinum nanoparticles. The precursors are characterized and their thermal properties are studied by thermogravimetric analysis (TGA) and infrared (IR). Investigations of the precursor decomposition mechanism, the effect of oxygen, and the autocatalytic effect during CVD are also carried out. Finally, transmission electron microscopy (TEM) and X-ray photoelectron spectroscopy (XPS) analyses prove that continuous CVS of gas-borne support particles combined with MOCVD of these newly synthesized platinum precursors gives ordered, defined platinum nanocatalysts with high dispersion and narrow size distribution (2 À 3 nm).

The Cu-catalyzed azide-alkyne cycloaddition (CuAAC) reaction is a cornerstone method for the ligation of biomolecules. However, undesired Cu-mediated oxidation and Cu-contamination in bioconjugates limits biomedical utility. Here, we report a generic CuAAC flow platform for the rapid, robust, and broad-spectrum formation of discrete triazole bioconjugates. This process leverages an engineering problem to chemical advantage: solvent-mediated Cu pipe erosion generates ppm levels of Cu in situ under laminar flow conditions. This is sufficient to catalyze the CuAAC reaction of small molecule alkynes and azides, fluorophores, marketed drug molecules, peptides, DNA, and therapeutic oligonucleotides. This flow approach, not replicated in batch, operates at ambient temperature and pressure, requires short residence times, avoids oxidation of sensitive functional groups, and produces products with very low ppm Cu contamination.