Ligands with polyfluorophenyl moieties promote a local structural rearrangement in the Spinach2 and Broccoli aptamers that increases ligand affinities.

The interaction of nucleic acids with their molecular targets often involves structural reorganization that may traverse a complex folding landscape. With the more recent recognition that many RNAs, both coding and noncoding, may regulate cellular activities by interacting with target molecules, it becomes increasingly important to understand how nucleic acids interact with their targets and how drugs might be developed that can influence critical folding transitions. We have extensively investigated the interaction of the Spinach2 and Broccoli aptamers with a library of small molecule ligands modified by various extensions from the imido nitrogen of DFHBI [(Z)-5-(3,5-difluoro-4-hydroxybenzylidene)-2,3-dimethyl-3,5-dihydro-4H-imidazol-4-one] that reach out from the Spinach2 ligand binding pocket.

Synthesis, Fabrication, and Characterization of Functionalized Polydiacetylene Containing Cellulose Nanofibrous Composites for Colorimetric Sensing of Organophosphate Compounds.

Organophosphate (OP) compounds, a family of highly hazardous chemical compounds included in nerve agents and pesticides, have been linked to more than 250,000 annual deaths connected to various chronic diseases. However, a solid-state sensing system that is able to be integrated into a clothing system is rare in the literature. This study aims to develop a nanofiber-based solid-state polymeric material as a soft sensor to detect OP compounds present in the environment.

Characterization of a Cytosolic Acyl-Activating Enzyme Catalyzing the Formation of 4-Methylvaleryl-CoA for Pogostone Biosynthesis in Pogostemon Cablin.

Pogostone, a compound with various pharmaceutical activities, is a major constituent of the essential oil preparation called Pogostemonis Herba, which is obtained from the plant Pogostemon cablin. The biosynthesis of pogostone has not been elucidated, but 4-methylvaleryl-CoA (4MVCoA) is a likely precursor. We analyzed the distribution of pogostone in P.

Ozonolysis of Alkynes-A Flexible Route to Alpha-Diketones: Synthesis of AI-2.

A mild procedure for the low-temperature conversion of alkynes to diketones has been developed and employed in the synthesis of AI-2.

Direct Synthesis of the Phenanthroviridone Skeleton Using a Highly Regioselective Nitroquinone Diels-Alder Reaction.

A variety of nucleophiles react efficiently with in situ generated nitroquinones. The reaction with substituted resorcinols led to the direct synthesis of the phenanthroviridinone and lagumycin skeleton via a highly regioselective Diels-Alder reaction.

A Synthesis of Dihydro Eurotiumide B via a Tandem Butenolide Annulation/Reductive Thiolation Reaction.

Dihydro eurotiumide B was prepared from a 5-phenylthiobutenolide via a tandem annulation/reductive thiolation reaction.

Characterization of the Photophysical Behavior of DFHBI Derivatives: Fluorogenic Molecules that Illuminate the Spinach RNA Aptamer.

( Z)-5-(3,5-Difluoro-4-hydroxybenzylidene)-2,3-dimethyl-3,5-dihydro-4 H-imidazol-4-one (DFHBI) and its analogues are fluorogenic molecules that bind the Spinach aptamer (a small RNA molecule), which was selected for imaging RNA. They are extremely weakly fluorescent in liquid solvents. It had been hypothesized that photoisomerization is a very efficient nonradiative process of deactivation.

Synthesis of (±)-Naphthacemycin A.

Naphthacemycin A was synthesized in nine steps by a sequence featuring a Diels-Alder reaction of a hindered aryl butadiene and a Hauser-Kraus annulation reaction.

Identification and characterization of small molecule inhibitors of porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome virus (PRRSV) is the etiological agent of PRRS, an economically significant disease of swine worldwide. PRRSV is poorly controlled by the currently available vaccines, and alternative control strategies are needed to help prevent the continual circulation of the virus. Previously, we developed a synthetic route for the natural compound atractylodinol and demonstrated anti-PRRSV activity in vitro.

Synthetic Anthocyanidins from Natural Benzopyrans.

A hydride abstraction strategy can be used to make anthocyanidins and isoflavylium salts from benzopyrans in good yields.

Specificity and Ligand Affinities of the Cocaine Aptamer: Impact of Structural Features and Physiological NaCl.

The cocaine aptamer has been seen as a good candidate for development as a probe for cocaine in many contexts. Here, we demonstrate that the aptamer binds cocaine, norcocaine, and cocaethylene with similar affinities and aminoglycosides with similar or higher affinities in a mutually exclusive manner with cocaine. Analysis of its affinities for a series of cocaine derivatives shows that the aptamer specificity is the consequence of its interaction with all faces of the cocaine molecule.

Light-up and FRET aptamer reporters; evaluating their applications for imaging transcription in eukaryotic cells.

The regulation of RNA transcription is central to cellular function. Changes in gene expression drive differentiation and cellular responses to events such as injury. RNA trafficking can also have a large impact on protein expression and its localization.

Phthalide Anions in Organic Synthesis. A Direct Total Synthesis of Furomollugin.

Furomollugin was synthesized in three steps from commercially available starting materials using phthalide annulation chemistry.

Live-cell imaging of Pol II promoter activity to monitor gene expression with RNA IMAGEtag reporters.

We describe a ribonucleic acid (RNA) reporter system for live-cell imaging of gene expression to detect changes in polymerase II activity on individual promoters in individual cells. The reporters use strings of RNA aptamers that constitute IMAGEtags (Intracellular MultiAptamer GEnetic tags) that can be expressed from a promoter of choice. For imaging, the cells are incubated with their ligands that are separately conjugated with one of the FRET pair, Cy3 and Cy5.

Synthetic approach to the psoracorylifols.

Core analogs of the psoracorylifols were generated by a five-step route from 2,2-dimethyl-4-cyanobutanal.

First inverse electron-demand Diels-Alder methodology of 3-chloroindoles and methyl coumalate to carbazoles.

The first successful inverse electron-demand Diels-Alder has been demonstrated with the 2-pyrone methyl coumalate in conjunction with substituted indoles. Utilizing 1-alkyl-3-chloroindoles as the electron-rich dienophile efficiently generates carbazoles without the need for additional metal catalysts. Through a thermal, one-pot Diels-Alder/decarboxylation/elimination domino sequence, access to a class of 3-methylcarbazoles is rapidly generated with exclusive regiocontrol in up to 90% yield.

Synthesis of 3-farnesyl salicylic acid, a novel antimicrobial from Piper multiplinervium.

Both 3-farnesyl salicylic acid and 3-geranyl salicylic acid were synthesized from 2,6-dibromophenol and showed low levels of antimicrobial activity against E. coli strains.

Mechanistic insights into ring-opening and decarboxylation of 2-pyrones in liquid water and tetrahydrofuran.

2-Pyrones, such as triacetic acid lactone, are a promising class of biorenewable platform chemicals that provide access to an array of chemical products and intermediates. We illustrate through the combination of results from experimental studies and first-principle density functional theory calculations that key structural features dictate the mechanisms underlying ring-opening and decarboxylation of 2-pyrones, including the degree of ring saturation, the presence of C═C bonds at the C4═C5 or C5═C6 positions within the ring, as well as the presence of a β-keto group at the C4 position. Our results demonstrate that 2-pyrones undergo a range of reactions unique to their structure, such as retro-Diels-Alder reactions and nucleophilic addition of water.

Total synthesis of paracaseolide A.

The total synthesis of paracaseolide A, a valuable cell-cycle progression inhibitor, was accomplished in 8 steps from known compounds, with 6.6% overall yield. The synthetic strategy creates strong potential for diversification.

Synthesis of uliginosins A and B.

The uliginosins have potentially very useful biological activity, but their availability from natural sources is limited. Moreover, the one synthesis can not be reproduced. Here we report reproducible conditions for the synthesis of the uliginosins.

Effect of a mitochondria-targeted vitamin E derivative on mitochondrial alteration and systemic oxidative stress in mice.

The objective of the present study was to determine whether a mitochondria-targeted vitamin E derivative (MitoVit E) would affect certain mitochondrial parameters, as well as systemic oxidative stress. A total of sixty-four mice were fed a high-fat (HF) diet for 5 weeks. They were then switched to either a low-fat (LF) or a medium-fat (MF) diet, and administered orally with MitoVit E (40 mg MitoVit E/kg body weight) or drug vehicle (10 % (v/v) ethanol in 0·9 % (w/v) NaCl solution), every other day for 5 weeks.

Synthesis of chroman aldehydes that inhibit HIV.

Chroman aldehydes bearing an acetyl group plus alkoxyl or hydroxyl groups inhibit HIV infectivity in HeLa37 cells.

Synthesis of azafluorenone antimicrobial agents.

A flexible synthesis of the azafluorenone alkaloids 1, 2, 3, and 4 is described.

Divergent approach to flavones and aurones via dihaloacrylic acids. Unexpected dependence on the halogen atom.

The reaction of phenols with 7a led to the synthesis of aurones, while the reaction of phenols with 7b led to the synthesis of flavones.

New effective inhibitors of the Abelson kinase.

The effects of substituents on the aryl ring were studied by the preparation and testing of several PD173955 analogs. Inserting a single carbon atom into the C-N bond in the aniline subunit (PDC) reduced the kinase inhibition by a factor of 200. Despite its decreased affinity for Abl compared with PD173955, PDC exhibits a Ki very similar to that reported for Imatinib.