High-Throughput Optimization of Photochemical Reactions using Segmented-Flow Nanoelectrospray-Ionization Mass Spectrometry.

Within the realm of drug discovery, high-throughput experimentation techniques enable the rapid optimization of reactions and expedited generation of drug compound libraries for biological and pharmacokinetic evaluation. Herein we report the development of a segmented flow mass spectrometry-based platform to enable the rapid exploration of photoredox reactions for early-stage drug discovery. Specifically, microwell plate-based photochemical reaction screens were reformatted to segmented flow format to enable delivery to nanoelectrospray ionization-mass spectrometry analysis.

Phenotypic screen identifies calcineurin-sparing FK506 analogs as BMP potentiators for treatment of acute kidney injury.

Acute kidney injury (AKI) is a life-threatening disease with no known curative or preventive therapies. Data from multiple animal models and human studies have linked dysregulation of bone morphogenetic protein (BMP) signaling to AKI. Small molecules that potentiate endogenous BMP signaling should have a beneficial effect in AKI.

Design of a Compliant Mechanism Based Four-Stage Amplification Piezoelectric-Driven Asymmetric Microgripper.

The existing symmetrical microgrippers have larger output displacements compared with the asymmetrical counterparts. However, the two jaws of a symmetrical microgripper are less unlikely to offer the same forces on the two sides of a grasped micro-object due to the manufacture and assembly errors. Therefore, this paper proposes a new asymmetric microgripper to obtain stable output force of the gripper.

High prevalence of CTX-M belonging to ST410 and ST889 among ESBL producing E. coli isolates from waterfowl birds in China's tropical island, Hainan.

The epidemiology and genetic characteristics of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (E. coli) have been widely studied in human and veterinary settings. ESBL-producing E.

Optimal flip angle for robust practical quantitative NMR measurement using a fixed pulse length.

NMR quantification has been traditionally performed by using internal standards. Although methods using external reference in NMR quantification have been developed, the major obstacles in using external referencing method are the measurement deviations associated with changing sample conditions and the requirement of pulse width calibration for every sample in order to compensate these errors. The calibration process is time consuming and in some cases impossible.

Kriging modeling and SPSA adjusting PID with KPWF compensator control of IPMC gripper for mm-sized objects.

Ionic polymer metal composite (IPMC) as a new smart material has been widely concerned in the micromanipulation field. In this paper, a novel two-finger gripper which contains an IPMC actuator and an ultrasensitive force sensor is proposed and fabricated. The IPMC as one finger of the gripper for mm-sized objects can achieve gripping and releasing motion, and the other finger works not only as a support finger but also as a force sensor.

In-tube derivatization for determination of absolute configuration and enantiomeric purity of chiral compounds by NMR spectroscopy.

We have developed an in-tube derivatization method using commercially available polymer-supported coupling agents to prepare derivatives of chiral compounds directly in NMR tube with high yield and purity. Because the method does not require any workup or purification, the configuration and enatiopurity can be quickly determined by NMR analysis for a small amount of chiral compounds, which is critical for today's fast-paced medicinal chemistry efforts in drug discovery. The application of the method was demonstrated for the derivatization of chiral amines, alcohols, diols, amino alcohols, thiols, and carboxylic acids using various chiral derivatizing agents and coupling agents.

Evaluation of solvent effects on protonation using NMR spectroscopy: implication in salt formation.

Investigation of the use of solution NMR spectroscopy to determine the effect of organic solvents on chemical shift changes in bases on addition of acids is reported. This information can be useful in the evaluation of solvents and counterion selection for salt formation. (1)H and (15)N chemical shift changes in three bases (pyrazine, phthalazine, and pyridine) on the addition of acids (1:1 ratio) were determined in various solvents.

Suppression of HDAC nuclear export and cardiomyocyte hypertrophy by novel irreversible inhibitors of CRM1.

Histone deacetylase 5 (HDAC5) represses expression of nuclear genes that promote cardiac hypertrophy. Agonism of a variety of G protein coupled receptors (GPCRs) triggers phosphorylation-dependent nuclear export of HDAC5 via the CRM1 nuclear export receptor, resulting in derepression of pro-hypertrophic genes. A cell-based high-throughput screen of a commercial compound collection was employed to identify compounds with the ability to preserve the nuclear fraction of GFP-HDAC5 in primary cardiomyocytes exposed to GPCR agonists.

The use of MPA amide for the assignment of absolute configuration of a sterically hindered cyclic secondary amine by 'mix and shake' NMR method.

We present here a new method using methoxyphenylacetic acid (MPA) as the chiral derivatizing agent (CDA) for the assignment of absolute configuration of cyclic secondary amines. The MPA amides were prepared using the purification-free 'mix and shake' method. A detailed conformational analysis for the two diastereomeric amides was conducted by 2D NMR experiments and molecular mechanics calculations.

Citric acid cycle intermediates as ligands for orphan G-protein-coupled receptors.

The citric acid cycle is central to the regulation of energy homeostasis and cell metabolism. Mutations in enzymes that catalyse steps in the citric acid cycle result in human diseases with various clinical presentations. The intermediates of the citric acid cycle are present at micromolar concentration in blood and are regulated by respiration, metabolism and renal reabsorption/extrusion.