Fluorous methods for the synthesis of peptides and oligonucleotides.

The non-covalent affinity of a perfluoro chain towards similar has been exploited by many to separate fluorous tagged compounds from non-fluorous compounds by F-SPE or F-LLE. This purification strategy found its application across diverse fields including peptide and oligonucleotide synthesis where even slight inefficient couplings result in deletion sequences that are often difficult to remove from the target sequence. Two commonly employed strategies to address this problem involve end-tagging the target sequence or capping the deletion sequences with fluorous tags.

Complete transfer of chirality in an intramolecular, thermal [2 + 2] cycloaddition of allene-ynes to form non-racemic spirooxindoles.

A thermal [2 + 2] cycloaddition reaction of allene-ynes has been used to transform chiral non-racemic allenyl oxindoles into chiral non-racemic spirooxindoles containing an alkylidene cyclobutene moiety. The enantiomeric excesses were determined by chiral lanthanide shift NMR analysis and the transfer of chiral information from the allene to the spirooxindole was found to be greater than 95%.

Chemical methodology as a source of small-molecule checkpoint inhibitors and heat shock protein 70 (Hsp70) modulators.

Unique chemical methodology enables the synthesis of innovative and diverse scaffolds and chemotypes and allows access to previously unexplored "chemical space." Compound collections based on such new synthetic methods can provide small-molecule probes of proteins and/or pathways whose functions are not fully understood. We describe the identification, characterization, and evolution of two such probes.

Lipid domains in bicelles containing unsaturated lipids and cholesterol.

We have created a stable bicelle system capable of forming micrometer-scale lipid domains that orient in a magnetic field, suitable for structural biology determination in solid-state NMR. The bicelles consisted of a mixture of cholesterol, saturated lipid (DMPC), and unsaturated lipid (POPC), a mixture commonly used to create domains in model membranes, along with a short chain lipid (DHPC) that allows formation of the bicelle phase. While maintaining a constant molar ratio of long to short chain lipids, q = ([POPC]+[DMPC])/[DHPC] = 3, we varied the concentrations of the unsaturated lipid, POPC, and cholesterol to observe the effects of the components on bicelle stability.

Tear glucose analysis for the noninvasive detection and monitoring of diabetes mellitus.

One approach to the noninvasive monitoring of blood glucose concentration is to monitor glucose concentrations in tear fluid. While several methods for sensing glucose in tear fluid have been proposed, controversy remains as to the precise concentrations of tear glucose in normal and diabetic subjects and as to whether tear fluid glucose concentrations correlate with blood glucose concentrations. This review covers the present understanding of the physiology of glucose transport in tears, the regulation of the aqueous tear fraction, and studies of tear glucose concentration over the last 80 years.

Photonic crystal sensor for organophosphate nerve agents utilizing the organophosphorus hydrolase enzyme.

We developed an intelligent polymerized crystalline colloidal array (IPCCA) photonic crystal sensing material which reversibly senses the organophosphate compound methyl paraoxon at micromolar concentrations in aqueous solutions. A periodic array of colloidal particles is embedded in a poly-2-hydroxyethylacrylate hydrogel. The particle lattice spacing is such that the array Bragg-diffracts visible light.

Cation identity dependence of crown ether photonic crystal Pb2+ sensing.

We quantitatively modeled the volume phase transition of a hydrogel containing a crystalline colloidal array with a crown ether ligand which binds Pb2+. The hydrogel volume response and the wavelength diffracted depend on the Pb2+ concentration and on both the ionic strength and the valence of the nonbinding ionic species. We successfully modeled the response of this hydrogel Pb2+ sensor to ionic strength and the cation valence of the added salts.

Binding of copper(II) to thyrotropin-releasing hormone (TRH) and its analogs.

Spectroscopy (UV-Vis, (1)H NMR, ESR) and electrochemistry revealed details of the structure of the Cu(II)-TRH (pyroglutamyl-histidyl-prolyl amide) complex. The (1)H NMR spectrum of TRH has been assigned. NMR spectra of TRH in the presence of Cu(II) showed that Cu(II) initially binds TRH through the imidazole.

Low-lying isomers and finite temperature behavior of (H2O)6 -.

(H2O)(6) (-) appears as a "magic" number water cluster in (H2O)(n) (-) mass spectra. The structure of the (H2O)(6) (-) isomer dominating the experimental population has been established only recently [N. I.

Controlling the electrochemically active area of carbon fiber microelectrodes by the electrodeposition and selective removal of an insulating photoresist.

A new and simple method permits control of the electrochemically active area of a carbon fiber microelectrode. An electrophoretic photoresist insulates the 10-microm-diameter carbon fiber microelectrodes. Photolysis of the photoresist followed by immersion of the exposed area into a developing solution reveals electroactive carbon fiber surface.

Progress toward the development of a point-of-care photonic crystal ammonia sensor.

We have developed an ammonia-sensitive material by coupling the Berthelot reaction to our polymerized crystalline colloidal array (PCCA) technology. The material consists of a periodic array of highly charged colloidal particles (110 nm diameter) embedded in a poly(hydroxyethyl acrylate) hydrogel. The particles have a lattice spacing such that they Bragg-diffract visible light.

Electron binding motifs of (H2O)n- clusters.

It is has been established that the excess electrons in small (i.e., n < or = 7) (H2O)n- clusters are bound in the dipole field of the neutral cluster and, thus, exist as surface states.

Measurement of association and dissociation rate constants for lead(II)/18-crown-6 using square wave voltammetry at a glassy carbon mercury film electrode.

Understanding the rate parameters of metal ion-ligand complexes is necessary for sensing, separations, and responsive materials. The complexation between 18-crown-6 and lead(II) is of particular interest due to the potential use of this chemistry in sensors and separations. We have applied square wave voltammetry at a glassy carbon mercury film electrode to this problem.

Quantum Drude oscillator model for describing the interaction of excess electrons with water clusters: an application to (H2O)13(-).

Cluster anions for which the excess electron occupies an extended nonvalence orbital can be described by use of a model Hamiltonian employing quantum Drude oscillators to represent the polarizable charge distributions of the monomers. In this work, a Drude model for water cluster anions is described and used to investigate the (H2O)13(-) cluster. Several low-energy isomers are characterized, and the finite-temperature properties of the cluster are investigated by means of parallel tempering Monte Carlo simulations.

Online preconcentration of thyrotropin-releasing hormone (TRH) by SDS-modified reversed phase column for microbore and capillary high-performance liquid chromatography (HPLC).

Thyrotropin-releasing hormone (TRH, pGlu-His-Pro-amide) is an important tripeptide existing in biological systems at low concentrations. It is a fairly hydrophilic peptide, cationic in acidic solutions. Preconcentration online before reversed phase chromatography separation can enhance concentration detection limits of hydrophobic, but not hydrophilic species.

Influence of chemical kinetics on postcolumn reaction in a capillary Taylor reactor with catechol analytes and photoluminescence following electron transfer.

Postcolumn derivatization reactions can enhance detector sensitivity and selectivity, but their successful combination with capillary liquid chromatography has been limited because of the small peak volumes in capillary chromatography. A capillary Taylor reactor (CTR), developed in our laboratory, provides simple and effective mixing and reaction in a 25-microm-radius postcolumn capillary. Homogenization of reactant streams occurs by radial diffusion, and a chemical reaction follows.

Acetylcholinesterase-based organophosphate nerve agent sensing photonic crystal.

We developed a polymerized crystalline colloidal array (PCCA) photonic crystal sensing material that senses the organophosphorus compound parathion at ultratrace concentrations in aqueous solutions. A periodic array of colloidal particles is embedded in a hydrogel network with a lattice spacing such that it Bragg diffracts visible light. The molecular recognition agent for the sensor is the enzyme acetylcholinesterase (AChE), which binds organophosphorus compounds irreversibly, creating an anionic phosphonyl species.

Photonic crystal glucose-sensing material for noninvasive monitoring of glucose in tear fluid.

Background: We recently developed a photonic crystal glucose-sensing material, which consists of a crystalline colloidal array embedded within a polymer network of a polyacrylamide-poly(ethylene glycol) hydrogel with pendent phenylboronic acid groups. The aim of the present work was to improve this approach for application to noninvasive or minimally invasive monitoring of glucose.

Methods: We used new boronic acid derivatives such as 4-amino-3-fluorophenylboronic acid and 4-carboxy-3-fluorophenylboronic acid as the molecular recognition elements to achieve sensing at physiologic pH values.

Analysis of the performance of a flow reactor for use with microcolumn HPLC.

Postcolumn derivatization reactions can be used to improve detector sensitivity or selectivity. The advantages of capillary chromatography for trace analysis could be augmented if there were postcolumn reactors suitable for microchromatographic systems. However, postcolumn derivatization is a challenge because of the small peak volumes associated with capillary columns.

High ionic strength glucose-sensing photonic crystal.

We demonstrate a colorimetric glucose recognition material consisting of a crystalline colloidal array embedded within a polyacrylamide-poly(ethylene glycol) (PEG) hydrogel, or a polyacrylamide-15-crown-5 hydrogel, with pendent phenylboronic acid groups. We utilize a new molecular recognition motif, in which boronic acid and PEG (or crown ether) functional groups are prepositioned in a photonic crystal hydrogel, such that glucose self-assembles these functional groups into a supramolecular complex. The formation of the complex results in an increase in the hydrogel cross-linking, which for physiologically relevant glucose concentration blue shifts the photonic crystal diffraction.

Synthesis and biological assessment of simplified analogues of the potent microtubule stabilizer (+)-discodermolide.

An efficient, convergent and stereocontrolled synthesis of simplified analogues of the potent antimitotic agent (+)-discodermolide has been achieved and several small libraries have been prepared. In all the libraries, the discodermolide methyl groups at C14 and C16 and the C7 hydroxy group were removed and the lactone was replaced by simple esters. Other modifications introduced in each series of analogues were related to C11, C17 and C19 of the natural product.

Photonic crystal aqueous metal cation sensing materials.

We developed a polymerized crystalline colloidal array photonic material that senses metal cations in water at low concentrations (PCCACS). Metal cations such as Cu2+, Co2+, Ni2+, and Zn2+ bind to 8-hydroxyquinoline groups covalently attached to the PCCACS. At low metal concentrations ( View Article and Find Full Text PDF

Photonic crystal carbohydrate sensors: low ionic strength sugar sensing.

We developed a carbohydrate sensing material, which consists of a crystalline colloidal array (CCA) incorporated into a polyacrylamide hydrogel (PCCA) with pendent boronic acid groups. The embedded CCA diffracts visible light, and the PCCA diffraction wavelength reports on the hydrogel volume. This boronic acid PCCA responds to species containing vicinal cis diols such as carbohydrates.

Dual-specificity phosphatases as targets for antineoplastic agents.

Dual-specificity protein phosphatases are a subclass of protein tyrosine phosphatases that are uniquely able to hydrolyse the phosphate ester bond on both a tyrosine and a threonine or serine residue on the same protein. Dual-specificity phosphatases have a central role in the complex regulation of signalling pathways that are involved in cell stress responses, proliferation and death. Although this enzyme family is increasingly the target of drug discovery efforts in pharmaceutical companies, a summary of the salient developments in the biology and medicinal chemistry of dual-specificity phosphatases has been lacking.