Heterometallic polyhydride complexes containing yttrium hydrides with different Cp ligands: synthesis, structure, and hydrogen-uptake/release properties.

A new family of Y(4)/M(2) and Y(5)/M heterobimetallic rare-earth-metal/d-block-transition-metal-polyhydride complexes has been synthesized. The reactions of the tetranuclear yttrium-octahydride complex [{Cp''Y(μ-H)(2)}(4)(thf)(4)] (Cp'' = C(5)Me(4)H, 1-C(5)Me(4)H) with one equivalent of Group-6-metal-pentahydride complexes [Cp*M(PMe(3))H(5)] (M = Mo, W; Cp* = C(5)Me(5)) afforded pentanuclear heterobimetallic Y(4)/M-polyhydride complexes [{(Cp''Y)(4)(μ-H)(7)}(μ-H)(4)MCp*(PMe(3))] (M = Mo (2 a), W (2 b)). UV irradiation of compounds 2 a,b in THF gave PMe(3)-free complexes [{(Cp''Y)(4)(μ-H)(6)(thf)(2)}(μ-H)(5)MCp*] (M = Mo (3 a), W (3 b)).

Sustained delivery of siRNA from dopamine-coated stainless steel surfaces.

Dopamine, an adhesive protein can be covalently deposited onto biomaterials. In this study, we evaluated the ability of dopamine-coated surfaces for small interfering RNA (siRNA) immobilization and release. Dopamine was deposited onto 316L stainless steel discs either as a monolayer at acidic pH or as polydopamine at alkaline pH, following which siRNA was immobilized onto these discs.

Cationic cholesterol-modified gelatin as an in vitro siRNA delivery vehicle.

Polymeric micelle prepared through the self-assembly of cationic cholesterol-modified gelatin was tested for siRNA delivery. It exerted the desired effect of gene knockdown in HeLa cells stably expressing the luciferase gene and achieved a two-fold increase in the knockdown ability when compared to Lipofectamine® 2000. It was found that the polymeric micelle exhibited excellent stability and increased the biological stability of the siRNA in serum.

Expansion of the aptamer library from a "natural soup" to an "unnatural soup".

The possibility of evolving a commonly existing biomolecule into a variety of functional biomolecules has now been realized in the form of aptamers through the development of in vitro selection. In addition to their high affinity and high specificity for the desired targets, aptamers are easily synthesized chemically and can be modified for downstream applications. Although aptamers were originally selected from a library containing only natural components, the past decade has seen a wealth of new aptamers selected from libraries containing unnatural components to provide new aptamer functions artificially.

Clearance of yeast eRF-3 prion [PSI+] by amyloid enlargement due to the imbalance between chaperone Ssa1 and cochaperone Sgt2.

The cytoplasmic [PSI+] element of budding yeast represents the prion conformation of translation release factor eRF-3 (Sup35). Prions are transmissible agents caused by self-seeded highly ordered aggregates (amyloids). Much interest lies in understanding how prions are developed and transmitted.

Epidithiodiketopiperazine as a pharmacophore for protein lysine methyltransferase G9a inhibitors: reducing cytotoxicity by structural simplification.

Chaetocin (1), a structurally complex epidithiodiketopiperazine (ETP) alkaloid produced by Chaetomium minutum, is a potent inhibitor of protein lysine methyltransferase G9a, which plays important roles in many biological processes. Here we present our synthetic investigations to identify a simple prototype G9a inhibitor structure based on structure-activity relationship (SAR) studies on chaetocin derivatives. The simple derivative PS-ETP-1 (14) was found to be a potent G9a inhibitor with greatly reduced cytotoxicity.

Characterization and mechanism of glass microwelding by double-pulse ultrafast laser irradiation.

We investigated the physical mechanism of high-efficiency glass microwelding by double-pulse ultrafast laser irradiation by measuring the dependences of the size of the heat-affected zone and the bonding strength on the delay time between the two pulses for delay time up to 80 ns. The size of the heat-affected zone increases rapidly when the delay time is increased from 0 to 12.5 ps.

Morphobase, an encyclopedic cell morphology database, and its use for drug target identification.

Visual observation is a powerful approach for screening bioactive compounds that can facilitate the discovery of attractive druggable targets following their chemicobiological validation. So far, many high-content approaches, using sophisticated imaging technology and bioinformatics, have been developed. In our study, we aimed to develop a simpler method that focuses on intact cell images because we found that dynamic changes in morphology are informative, often reflecting the mechanism of action of a drug.

Terpendole E, a kinesin Eg5 inhibitor, is a key biosynthetic intermediate of indole-diterpenes in the producing fungus Chaunopycnis alba.

Terpendole E is the first natural product inhibitor of kinesin Eg5. Because terpendole E production is unstable, we isolated and analyzed the terpendole E biosynthetic gene cluster, which consists of seven genes encoding three P450 monooxygenases (TerP, TerQ, and TerK), an FAD-dependent monooxygenase (TerM), a terpene cyclase (TerB), and two prenyltransferases (TerC and TerF). Gene knockout and feeding experiments revealed that terpendole E is a key intermediate in terpendole biosynthesis and is produced by the action of the key enzyme TerQ from paspaline, a common biosynthetic intermediate of indole-diterpenes.

Preparation of cell-culturing glass surfaces that release branched polyethyleneimine triggered by thiol-disulfide exchange.

To develop a chemical stimulus-responsive substrate for culturing cells, polyethyleneimine (PEI) having a pyridyl disulfide moiety was attached via disulfide linkages to a glass coverslip modified with a silane coupling agent having a thiol group. The surface modification was confirmed by X-ray photoelectron spectroscopy and zeta potential analysis. The obtained surface exhibited sufficiently high cell adhesiveness.

Dynamic or nondynamic? Helical trajectory in hexabenzocoronene nanotubes biased by a detachable chiral auxiliary.

When ether vapor was allowed to diffuse into a CH(2)Cl(2) solution of an enantiomer of a hexa-peri-hexabenzocoronene (HBC) derivative carrying a chiral (BINAP)Pt(II)-appended coordination metallacycle (HBC(Py)([(R)-Pt]) or HBC(Py)([(S)-Pt])), screw-sense-selective assembly took place to give optically active nanotubes (NT(Py)([(R)-Pt]) or NT(Py)([(S)-Pt])) with helical chirality, which were enriched in either left-handed (M)-NT(Py)([(R)-Pt]) or right-handed (P)-NT(Py)([(S)-Pt]), depending on the absolute configuration of the (BINAP)Pt(II) pendant. When MeOH was used instead of ether for the vapor-diffusion-induced assembly, nanocoils formed along with the nanotubes. As determined by scanning electron microscopy, the diastereomeric excess of the nanocoils was 60% (80:20 diastereomeric ratio).

Molecular architecture and therapeutic potential of lectin mimics.

Lectins are proteins of non-immune origin that bind specific carbohydrates without chemical modification. Coupled with the emerging biological and pathological significance of carbohydrates, lectins have become extensively used as research tools in glycobiology. However, lectin-based drug development has been impeded by high manufacturing costs, low chemical stability, and the potential risk of initiating an unfavorable immune response.

Genetic PEGylation.

Polyethylene glycol (PEG) was genetically incorporated into a polypeptide. Stop-anticodon-containing tRNAs were acylated with PEG-containing amino acids and were then translated into polypeptides corresponding to DNA sequences containing the stop codons. The molecular weights of the PEG used were 170, 500, 700, 1000, and 2000 Da, and the translation was confirmed by mass spectrometry.

Confident identification of isomeric N-glycan structures by combined ion mobility mass spectrometry and hydrophilic interaction liquid chromatography.

Rationale: A central issue in glycan mass analysis is the ambiguity of structural assignments due to the heterogeneity and complexity of glycan structures. Ion mobility mass spectrometry (IM-MS) has the potential to separate isomeric glycans depending on their unique collisional cross section especially when coupled with hydrophilic interaction liquid chromatography (HILIC).

Methods: Ten pyridylaminated biantennary N-glycans including isomeric structures were measured by electrospray ionization quadrupole-time-of-flight mass spectrometry with an ion mobility phase.

The role of acetylation in the subcellular localization of an oncogenic isoform of translation factor eIF5A.

Mammalian cells express two isoforms of eIF5A, eIF5A1 and eIF5A2, but little is known about the function of eIF5A2. Here we report that eIF5A2 is reversibly acetylated at lysine-47. HDAC6 and SIRT2 were identified as the enzymes responsible for deacetylating eIF5A2.

In vitro selection of a photo-responsive peptide aptamer using ribosome display.

A photo-responsive peptide aptamer against microbeads immobilized streptavidin was isolated using in vitro selection combined with photo-manipulation. This is the first example of the introduction of a peptide aptamer in the photo-control of dynamic molecular recognition.

Real-Time XRD Studies of Li-O2 Electrochemical Reaction in Nonaqueous Lithium-Oxygen Battery.

Understanding of electrochemical process in rechargeable Li-O2 battery has suffered from lack of proper analytical tool, especially related to the identification of chemical species and number of electrons involved in the discharge/recharge process. Here we present a simple and straightforward analytical method for simultaneously attaining chemical and quantified information of Li2O2 (discharge product) and byproducts using in situ XRD measurement. By real-time monitoring of solid-state Li2O2 peak area, the accurate efficiency of Li2O2 formation and the number of electrons can be evaluated during full discharge.

Quantitative single-nucleotide polymorphism analysis in secondary-structured DNA by affinity capillary electrophoresis using a polyethylene glycol-peptide nucleic acid block copolymer.

To estimate allele frequency of single-nucleotide polymorphisms (SNPs) in pooled DNAs with secondary structures, an affinity capillary electrophoresis was developed using an allele-specific peptide nucleic acid probe modified with polyethylene glycol. This probe disrupted secondary structures of DNA analytes and hybridized to them during electrophoresis. Such DNA-binding capability allowed separation of the folded analytes with a single-base difference within 20 min.

Lipoproteins in bacteria: structures and biosynthetic pathways.

Bacterial lipoproteins are characterized by the presence of a conserved N-terminal lipid-modified cysteine residue that allows the hydrophilic protein to anchor onto bacterial cell membranes. These proteins play important roles in a wide variety of bacterial physiological processes, including virulence, and induce innate immune reactions by functioning as ligands of the mammalian Toll-like receptor 2. We review recent advances in our understanding of bacterial lipoprotein structure, biosynthesis and structure-function relationships between bacterial lipoproteins and Toll-like receptor 2.

Soluble amyloid precursor protein 770 is released from inflamed endothelial cells and activated platelets: a novel biomarker for acute coronary syndrome.

Background: Separate monitoring of the cleavage products of different amyloid β precursor protein (APP) variants may provide useful information.

Results: We found that soluble APP770 (sAPP770) is released from inflamed endothelial cells and activated platelets as judged by ELISA.

Conclusion: sAPP770 is an indicator for endothelial and platelet dysfunctions.

Two-dimensional Heisenberg behavior of J(eff)=1/2 isospins in the paramagnetic state of the spin-orbital Mott insulator Sr2IrO4.

The dynamical correlations of J(eff)=1/2 isospins in the paramagnetic state of spin-orbital Mott insulator Sr2IrO4 were revealed by resonant magnetic x-ray diffuse scattering. We found a two-dimensional antiferromagnetic fluctuation with a large in-plane correlation length exceeding 100 lattice spacings at even 20 K above the magnetic ordering temperature. In marked contrast to the naive expectation of the strong magnetic anisotropy associated with an enhanced spin-orbit coupling, we discovered an isotropic isospin correlation that is well described by the two-dimensional S=1/2 quantum Heisenberg model.