Protein tyrosine phosphatase 1B inhibitors from a marine-derived fungal strain aspergillus sp. SF-5929

Abstract

In the course of our continuing investigation of bioactive secondary metabolites from marine-derived fungal strains, a racemate of a novel diphenolic derivative named (±)-tylopilusin D (1) along with ten previously known secondary metabolites (2–11) were isolated from a marine-derived fungal strain Aspergillus sp. SF-5929. Their structures were elucidated mainly by analysis of NMR and MS data. In addition, the inhibitory effects of the isolated compounds against protein tyrosine phosphatase 1B (PTP1B) activity were evaluated, and compounds 1, 2, and 5–7 inhibited PTP1B activity with IC₅₀ values ranging from 3.3 to 8.1?µM. Kinetics studies suggested that compounds 1, 2, and 5 had noncompetitive inhibitory effects against PTP1B.     

Plasmonic Hotspots in Air: An Omnidirectional Three‐Dimensional Platform for Stand‐Off In‐Air SERS Sensing of Airborne Species

Molecular‐level airborne sensing is critical for early prevention of disasters, diseases, and terrorism. Currently, most 2D surface‐enhanced Raman spectroscopy (SERS) substrates used for air sensing have only one functional surface and exhibit poor SERS‐active depth. “Aerosolized plasmonic colloidosomes” (APCs) are introduced as airborne plasmonic hotspots for direct in‐air SERS measurements. APCs function as a macroscale 3D and omnidirectional plasmonic cloud that receives laser irradiation and emits signals in all directions. Importantly, it brings about an effective plasmonic hotspot in a length scale of approximately 2.3 cm, which affords 100‐fold higher tolerance to laser misalignment along the z‐axis compared with 2D SERS substrates. APCs exhibit an extraordinary omnidirectional property and demonstrate consistent SERS performance that is independent of the laser and analyte introductory pathway. Furthermore, the first in‐air SERS detection is demonstrated in stand‐off conditions at a distance of 200 cm, highlighting the applicability of 3D omnidirectional plasmonic clouds for remote airborne sensing in threatening or inaccessible areas.     

Microarray-based detection of Korean-specific <Emphasis Type="Italic">BRCA1</Emphasis> mutations

A reliable multiplex assay procedure to detect human genetic mutations in the breast cancer susceptibility gene BRCA1 using zip-code microarrays and single base extension (SBE) reactions is described. Multiplex PCR amplification was performed to amplify the genomic regions containing the mutation sites. The PCR products were then employed as templates in subsequent multiplex SBE reactions using bifunctional primers carrying a unique complementary zip sequence in addition to a mutation-site-specific sequence. The SBE primers, terminating one base before their mutation sites, were extended by a single base at a mutation site with a corresponding biotin-labeled ddNTP. Hybridization of the SBE products to zip-code microarrays was followed by staining with streptavidin–Cy3, leading to successful genotyping of several selected BRCA1 mutation sites with wild-type and heterozygote mutant samples from breast cancer patients. This work has led to the development of a reliable DNA microarray-based system for the diagnosis of human genetic mutations. Cheulhee Jung and Seong-Chun Yim contributed equally to this work.     

Change in the interfacial reaction of Hf-silicate film as a function of thickness and stoichiometry

Medium energy ion scattering and high-resolution transmission electron microscopy are used to investigate the depth of the interfacial reaction of Hf-silicate film. The interfacial reaction is critically affected by the film thickness and the mole fraction of HfO(2) in silicate film. The interfacial compressive strain generated at the surface of the Si substrate is dependent on the film thickness during the postannealing process in film with a thickness of approximately 4 nm. Finally, the phase separation phenomenon demonstrates critically different behaviors at different film thicknesses and stoichiometries because the diffusion of Si from interface to surface is dependent on these factors. Moreover, the oxidation by oxygen impurity in the inert ambient causes SiO(2) top formation.     

A facile synthesis of 1‐alkyl‐5‐arylalkoxy‐6‐methoxy‐3,4‐dihydroisoquinolines

1‐Alkyl‐5‐arylalkoxy‐6‐methoxy‐3,4‐dihydroisoquinolines were synthesized by the alkylation of 1‐alkyl‐5‐hydroxy‐6‐methoxy‐3,4‐dihydroisoquinolines with arylalkyl halide in the presence of potassium carbonate. 1‐Alkyl‐5‐hydroxy‐6‐methoxy‐3,4‐dihydroisoquinolines as key precursor prepared from o‐vaniline via 6 steps.     

Calibration method for ESR signal intensity of calcitic shells

A practical method of calibrating intensities of ESR signals with a single crystal of copper pentahydrate (CuSO₄ · 5H₂O) has been developed for calcitic shells containing a large amount of manganese (Mn²⁺). A sample holder is designed to insert the crystal from the bottom of the cavity for use as a standard sample. The signal of Cu²⁺ in the standard does not interfere with the Mn²⁺ signals. The Cu²⁺ signal and dating signal of the shell are recorded simultaneously; the ratio of their intensities is the basis for calibration. It is shown that this calibration method reduces the errors attributed to both coupling and unloadedQ factors of the cavity resonator to within 2%.     

Evaluation of the internal temperatures of an 8.6 kDa protein cation exposed to a hot dispenser cathode employed in electron capture dissociation mass spectrometry

The 'effective' internal temperature of an 8.6 kDa ubiquitin cation was estimated under electron capture dissociation (ECD) conditions, in which a dispenser cathode electron source was mounted just outside an ion cyclotron resonance (ICR) cell, i.e., axially displaced at a distance less than 1 cm from the rear trap plate of the ICR cell. In this ECD configuration, thermal activation of the molecular ions stored in the ICR cell was anticipated since the heated dispenser cathode (T(cathode surface) > 1000 degrees C) emitted a large amount of (both visible and infrared) radiation as well as electrons. An evaluation of the internal temperature of ubiquitin 6+ and 7+ cations was made by comparing our ECD fragmentation patterns with those obtained by McLafferty et al. (J. Am. Chem. Soc. 2002; 124: 6407) as a function of the ion temperature. In McLafferty's configuration, the heating (or thermal activation) effect of their filament source was minimal since the filament was displaced by a distance as far as 70 cm from their ICR cell. A careful comparison reveals that the fragmentation patterns obtained in this work are very similar to those previously measured at T approximately 125 degrees C. In terms of sequence coverage, our ECD configuration provides better results, and in particular without the aid of any other simultaneous activation method, such as thermal heating, infrared multiphoton irradiation, or collisional activation, except for the visible and infrared radiation from the heated cathode.     

Increasing protein stability through control of the nanoscale environment

We have discovered a novel property of single-walled carbon nanotubes (SWNTs)-their ability to stabilize proteins at elevated temperatures and in organic solvents to a greater extent than conventional flat supports. Experimental results and theoretical analysis reveal that the stabilization results from the curvature of SWNTs, which suppresses unfavorable protein-protein lateral interactions. Our results also indicate that the phenomenon is not unique to SWNTs but could be extended to other nanomaterials. The protein-nanotube conjugates represent a new generation of active and stable catalytic materials with potential use in biosensors, diagnostics, and bioactive films and other hybrid materials that integrate biotic and abiotic components.