The archaeal family 3 polyphosphate kinase reveals a function of polyphosphate as energy buffer under low energy charge.

Inorganic polyphosphate, a linear polymer of orthophosphate residues linked by phosphoanhydride bonds, occurs in all three domains of life and plays a diverse and prominent role in metabolism and cellular regulation. While the polyphosphate metabolism and its physiological significance have been well studied in bacteria and eukaryotes including human, there are only few studies in archaea available so far. In Crenarchaeota including members of , the presence of polyphosphate and degradation via exopolyphosphatase has been reported and there is some evidence for a functional role in metal ion chelation, biofilm formation, adhesion and motility, however, the nature of the crenarchaeal polyphosphate kinase is still unknown.

Increased Cytotoxicity of Bimetallic Ultrasmall Silver-Platinum Nanoparticles (2 nm) on Cells and Bacteria in Comparison to Silver Nanoparticles of the Same Size.

Ultrasmall nanoparticles (diameter 2 nm) of silver, platinum, and bimetallic nanoparticles (molar ratio of Ag:Pt 0:100; 20:80; 50:50; 70:30; 100:0), stabilized by the thiolated ligand glutathione, were prepared and characterized by transmission electron microscopy, differential centrifugal sedimentation, X-ray photoelectron spectroscopy, small-angle X-ray scattering, X-ray powder diffraction, and NMR spectroscopy in aqueous dispersion. Gold nanoparticles of the same size were prepared as control. The particles were fluorescently labeled by conjugation of the dye AlexaFluor-647 via copper-catalyzed azide-alkyne cycloaddition after converting amine groups of glutathione into azide groups.

Merging of a Supramolecular Ligand with a Switchable Luminophore - Light-Responsiveness, Photophysics and Bioimaging.

In this contribution we report on a novel approach towards luminescent light-responsive ligands. To this end, cyanostilbene- guanidiniocarbonyl-pyrrole hybrids were designed and investigated. Merging of a luminophore with a supramolecular bioactive ligand bears numerous advantages by overcoming the typical drawbacks of drug-labelling, influencing the overall performance of the active species by attachment of a large luminophore.

Functional Linkers Support Targeting of Multivalent Tweezers to Taspase1.

Taspase 1 is a unique protease not only pivotal for embryonic development but also implicated in leukemias and solid tumors. As such, this enzyme is a promising while still challenging therapeutic target, and with its protein structure featuring a flexible loop preceding the active site a versatile model system for drug development. Supramolecular ligands provide a promising complementary approach to traditional small-molecule inhibitors.

The Molecular Footprint of Peptides on the Surface of Ultrasmall Gold Nanoparticles (2 nm) Is Governed by Steric Demand.

Ultrasmall gold nanoparticles were functionalized with peptides of two to seven amino acids that contained one cysteine molecule as anchor via a thiol-gold bond and a number of alanine residues as nonbinding amino acid. The cysteine was located either in the center of the molecule or at the end (C-terminus). For comparison, gold nanoparticles were also functionalized with cysteine alone.

Multivalent Molecular Tweezers Disrupt the Essential NDC80 Interaction with Microtubules.

Binding of microtubule filaments by the conserved Ndc80 protein is required for kinetochore-microtubule attachments in cells and the successful distribution of the genetic material during cell division. The reversible inhibition of microtubule binding is an important aspect of the physiological error correction process. Small molecule inhibitors of protein-protein interactions involving Ndc80 are therefore highly desirable, both for mechanistic studies of chromosome segregation and also for their potential therapeutic value.

Recognition of a Flexible Protein Loop in Taspase 1 by Multivalent Supramolecular Tweezers.

Many natural proteins contain flexible loops utilizing well-defined complementary surface regions of their interacting partners and usually undergo major structural rearrangements to allow perfect binding. The molecular recognition of such flexible structures is still highly challenging due to the inherent conformational dynamics. Notably, protein-protein interactions are on the other hand characterized by a multivalent display of complementary binding partners to enhance molecular affinity and specificity.

Phosphorescence Induction by Host-Guest Complexation with Cyclodextrins - The Role of Regioisomerism and Affinity.

We present an in-depth investigation of cyclodextrin complexes with guest compounds featuring complexation-induced room temperature phosphorescence (RTP) in aqueous solution. Very interestingly, only the complexed regioisomers bearing lateral substituents on meta-position show RTP, whereas the stronger host-guest systems with para-substituted dyes show no RTP features. The reported systems were investigated regarding their complexation behavior in water using isothermal titration calorimetry and mass spectrometry.

Mapping the Regioisomeric Space and Visible Color Range of Purely Organic Dual Emitters with Ultralong Phosphorescence Components: From Violet to Red Towards Pure White Light.

We mapped the entire visible range of the electromagnetic spectrum and achieved white light emission (CIE: 0.31, 0.34) by combining the intrinsic ns-fluorescence with ultralong ms-phosphorescence from purely organic dual emitters.

Metal-Ligand Interface and Internal Structure of Ultrasmall Silver Nanoparticles (2 nm).

Ultrasmall silver nanoparticles were prepared by reduction with NaBH and surface-terminated with glutathione (GSH). The particles had a solid core diameter of 2 nm as shown by transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS). NMR-DOSY gave a hydrodynamic diameter of 2 to 2.

All in One: Stimuli-Responsive, Efficient Mitotracking, and Single Source White Light Emission.

"All in one" type luminogens, possessing combined properties related to optical, materials, and biological implications, are of urgent demand today, mainly because of the combined application potential of such probes. To the best of our knowledge, until now, an "all in one" type white light emitter together with stimuli-responsive behavior and highly efficient mitochondrial-tracking ability has not been reported yet. In this contribution, for the first time, we have investigated a pair of luminogens exhibiting white light emission (CIE coordinates: 0.

What is the role of acid-acid interactions in asymmetric phosphoric acid organocatalysis? A detailed mechanistic study using interlocked and non-interlocked catalysts.

Organocatalysis has revolutionized asymmetric synthesis. However, the supramolecular interactions of organocatalysts in solution are often neglected, although the formation of catalyst aggregates can have a strong impact on the catalytic reaction. For phosphoric acid based organocatalysts, we have now established that catalyst-catalyst interactions can be suppressed by using macrocyclic catalysts, which react predominantly in a monomeric fashion, while they can be favored by integration into a bifunctional catenane, which reacts mainly as phosphoric acid dimers.

A combined experimental and modelling approach for the Weimberg pathway optimisation.

The oxidative Weimberg pathway for the five-step pentose degradation to α-ketoglutarate is a key route for sustainable bioconversion of lignocellulosic biomass to added-value products and biofuels. The oxidative pathway from Caulobacter crescentus has been employed in in-vivo metabolic engineering with intact cells and in in-vitro enzyme cascades. The performance of such engineering approaches is often hampered by systems complexity, caused by non-linear kinetics and allosteric regulatory mechanisms.

Dissociation of the Signaling Protein K-Ras4B from Lipid Membranes Induced by a Molecular Tweezer.

Oncogenic Ras mutations occur in more than 30 % of human cancers. K-Ras4B is the most frequently mutated isoform of Ras proteins. Development of effective K-Ras4B inhibitors has been challenging, hence new approaches to inhibit this oncogenic protein are urgently required.

Solution NMR Spectroscopy with Isotope-Labeled Cysteine (C and N) Reveals the Surface Structure of l-Cysteine-Coated Ultrasmall Gold Nanoparticles (1.8 nm).

Ultrasmall gold nanoparticles with a diameter of 1.8 nm were synthesized by reduction of tetrachloroauric acid with sodium borohydride in the presence of l-cysteine, with natural isotope abundance as well as C-labeled and N-labeled. The particle diameter was determined by high-resolution transmission electron microscopy and differential centrifugal sedimentation.

Molecular Tweezers with Additional Recognition Sites.

A new synthetic access to molecular tweezers with one or two aliphatic phosphate ester groups in the central benzene spacer-unit is presented. Alkynyl ester groups offer the prospect to attach additional functional units by click chemistry and greatly broaden the scope of these tools for chemical biology. We present two alternative strategies: the trichloroacetonitrile method involves activation of only one OH group of each phosphoric acid substituent by way of trichloroacetimidate intermediates and subsequent introduction of an aliphatic ester alcohol moiety.

Characterizing the Effect of Multivalent Conjugates Composed of Aβ-Specific Ligands and Metal Nanoparticles on Neurotoxic Fibrillar Aggregation.

Therapeutically active small molecules represent promising nonimmunogenic alternatives to antibodies for specifically targeting disease-relevant receptors. However, a potential drawback compared to antibody-antigen interactions may be the lower affinity of small molecules toward receptors. Here, we overcome this low-affinity problem by coating the surface of nanoparticles (NPs) with multiple ligands.

A nanomolar multivalent ligand as entry inhibitor of the hemagglutinin of avian influenza.

Influenza virus attaches itself to sialic acids on the surface of epithelial cells of the upper respiratory tract of the host using its own protein hemagglutinin. Species specificity of influenza virus is determined by the linkages of the sialic acids. Birds and humans have α2-3 and α2-6 linked sialic acids, respectively.

A nonionic inhibitor with high specificity for the UDP-Gal donor binding site of human blood group B galactosyltransferase: design, synthesis, and characterization.

9-(5-O-α-D-galactopyranosyl)-D-arabinityl-1,3,7-trihydropurine-2,6,8-trione (1) was designed and synthesized as a nonionic inhibitor for the donor binding site of human blood group B galactosyltransferase (GTB). Enzymatic characterization showed 1 to be extremely specific, as the highly homologous human N-acetylgalactosaminyltransferase (GTA) is not inhibited. The binding epitope of 1 demonstrates a high involvement of the arabinityl linker, whereas the galactose residue is only making contact to the protein via its C-2 site, which is very important for the discrimination between galactose and N-acetylgalactosamine, the substrate transferred by GTA.

Synthesis, structure, and photophysical properties of luminescent platinum(II) complexes containing cyclometalated 4-styryl-functionalized 2-phenylpyridine ligands.

A series of new luminescent cyclometalated platinum(II) complexes functionalized with various substituted styryl groups on the cyclometallating ligand [Pt(C/\N-ppy-4-styryl-R)(O/\O-(O)CCR'CHCR'C(O))] (ppy-4-styryl-R = E-4(4-(R)styryl-2-phenylpyridine) (3, R' = Me (acac); 4, R' = (t)Bu (dpm); R = H, OMe, NEt2, NO2) have been prepared. All complexes undergo an E-Z photoisomerization process in CH2Cl2 solution under sunlight, as monitored by 1H NMR. The solid-state structures of 3-OMe, 3-NEt2, 3-NO2, and 4-OMe have been determined by X-ray diffraction studies and compare well with optimized geometries obtained by density functional theory (DFT) calculations.