Structural basis for inhibition of protein tyrosine phosphatases by Keggin compounds phosphomolybdate and phosphotungstate

Protein-tyrosine phosphatases (PTPs) constitute a family of receptor-like, and cytoplasmic enzymes, which catalyze the dephosphorylation of phosphotyrosine residues in a variety of receptors and signaling molecules. Together with protein tyrosine kinases (PTKs), PTPs are critically involved in regulating many cellular signaling processes. In this study, diverse compounds were screened for PTP inhibition and selectively screened for inhibitors with the end product inhibition properties. Among phosphate analogues and their derivatives for PTP inhibition, Keggin compounds phosphomolybdate (PM) and phosphotungstate (PT) strongly inhibited both PTP-1B and SHP-1, with K(i) values of 0.06-1.2 micromM in the presence of EDTA. Unlike the vanadium compounds, inhibition potencies of PM and PT were not significantly affected by EDTA. PM and PT were potent, competitive inhibitors for PTPs, but relatively poor inhibitors of Ser/Thr phosphatase. Interestingly, PM and PT did not inhibit alkaline phosphatase at all. The crystal structure of PTP-1B in complex with PM, at 2.0 A resolution, reveals that MoO(3), derived from PM by hydrolysis, binds at the active site. The molybdenium atom of the inhibitor is coordinated with six ligands: three oxo-ligands, two apical water molecules and a S atom of the catalytic cysteine residue. In support of the crystallographic finding, we observed that molybdenium oxides (MoO(3), MoO(2), and MoO(2)Cl(2)) inhibited PTP-1B with IC(50) in the range 5-15 micromM.     

Reversed-phase liquid chromatographic method for the analysis of aminoglycoside antibiotics using pre-column derivatization with phenylisocyanate

A pre-column derivatization liquid chromatographic method has been developed for the analysis of aminoglycoside antibiotics using phenylisocyanate as a derivatization reagent. Derivatives including kanamycin, neomycin and gentamicin were formed by reaction of the analytes with phenylisocyanate in the presence of triethylamine. Phenylisocyanato groups were attached to corresponding amino groups of aminoglycoside and their molecular mass was confirmed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The experimental conditions for derivatization and separation of aminoglycoside derivatives were optimized and validated. A simple liquid chromatographic method for the determination of aminoglycoside antibiotics was demonstrated.     

Fabrication of nanocapsules with Au particles trapped inside carbon and silica nanoporous shells

Carbon capsules with hollow cores and mesoporous shells (HCMS) containing entrapped Au particles were prepared by template replication from solid core/mesoporous shell silica spheres with encapsulated Au particles. The resulting HCMS carbon capsules were then nanocast one step further to generate Au-trapping hollow core silica capsules with nanostructured shells.     

Phase‐transition characteristics of amphiphilic poly(2‐ethyl‐2‐oxazoline)/poly(ε‐caprolactone) block copolymers in aqueous solutions

Amphiphilic diblock and triblock copolymers of various block compositions based on hydrophilic poly(2‐ethyl‐2‐oxazoline) (PEtOz) and hydrophobic poly(ε‐caprolactone) were synthesized. The micelle formation of these block copolymers in aqueous media was confirmed by a fluorescence technique and dynamic light scattering. The critical micelle concentrations ranged from 35.5 to 4.6 mg/L for diblock copolymers and 4.7 to 9.0 mg/L for triblock copolymers, depending on the block composition. The phase‐transition behaviors of the block copolymers in concentrated aqueous solutions were investigated. When the temperature was increased, aqueous solutions of diblock and triblock copolymers exhibited gel–sol transition and precipitation, both of which were thermally reversible. The gel–sol transition‐ and precipitation temperatures were manipulated by adjustment of the block composition. As the hydrophobic portion of block copolymers became higher, a larger gel region was generated. In the presence of sodium chloride, the phase transitions were shifted to a lower temperature level. Sodium thiocyanate displaced the gel region and precipitation temperatures to a higher temperature level. The low molecular weight saccharides, such as glucose and maltose, contributed to the shift of phase‐transition temperatures to a lower temperature level, where glucose was more effective than maltose in lowering the gel–sol transition temperatures. The malonic acid that formed hydrogen bonds with the PEtOz shell of micelles was effective in lowering phase‐transition temperatures to 1.0M, above which concentration the block copolymer solutions formed complex precipitates. © 2000 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 38: 2400–2408, 2000     

Label‐Free Biosensing over a Wide Concentration Range with Photonic Force Microscopy

We present a label‐free biosensor that measures molecular interactions between biomolecules on the surface of a probe bead and substrate over a wide concentration range. This system is capable of detecting target biomolecules with concentrations varying from 10 nM to 0.1 pM , with high selectivity and sensitivity.     

Highly Stable,Water‐Dispersible Metal‐Nanoparticle‐Decorated Polymer Nanocapsules and Their Catalytic Applications

A facile synthesis of highly stable, water‐dispersible metal‐nanoparticle‐decorated polymer nanocapsules (M@CB‐PNs: M=Pd, Au, and Pt) was achieved by a simple two‐step process employing a polymer nanocapsule (CB‐PN) made of cucurbit[6]uril (CB[6]) and metal salts. The CB‐PN serves as a versatile platform where various metal nanoparticles with a controlled size can be introduced on the surface and stabilized to prepare new water‐dispersible nanostructures useful for many applications. The Pd nanoparticles on CB‐PN exhibit high stability and dispersibility in water as well as excellent catalytic activity and recyclability in carbon–carbon and carbon–nitrogen bond‐forming reactions in aqueous medium suggesting potential applications as a green catalyst.     

Conformation‐Specific Circular Dichroism Spectroscopy of Cold,Isolated Chiral Molecules

The CD spectroscopy of a chiral compound in solution yields an average CD value derived from all of the conformations of a chiral molecule. By contrast, CD spectroscopy of cold chiral molecules in the gas phase distinguishes specific conformers of a chiral molecule, but the weak CD effect has limited the practical application of this technique. Reported herein is the first resonant two‐photon ionization CD spectra of ephedrines in a supersonic jet using circularly polarized laser pulses, which were generated by synchronizing the oscillation of the photoelastic modulator with the laser firing. The spectra exhibited well‐resolved CD bands which were specific for the conformations and vibrational modes of each enantiomer. The CD signs and magnitudes of the jet‐cooled chiral molecules were very sensitive to their conformations and thus offered crucial information for determining the three‐dimensional structures of chiral species, as conducted in combination with quantum chemical calculations.