Improved lipid analysis using a 2D-LC-MS system with a novel injection procedure.

The aim of this study was to improve analysis of nonpolar lipidomics sample extracts using reversed phase (RP) chromatography. A 4/3/3 (v/v/v) mixture of methanol/methyl tert-butyl ether/chloroform (MeOH/MTBE/CHCl, MMC) was chosen for sample extraction solvent based on its proven extraction capability for several lipid classes. To avoid carry over, loss of analytes and peak distortion the loops and all capillaries of the presented LC system were flushed and filled up with methanol until the analytical column.

Small-scale two-dimensional liquid chromatography for a preparative re-purification of a highly labile tritium-labeled compound.

Tritium-labeled compounds are generally less stable than their non-labeled counterparts. This requires storage at low temperatures, a constant workflow of quality checks, and subsequent re-purifications. As the amount of tritium-labeled material is typically purified in the μg range, repeated injections on analytical-scale ultra high-performance liquid chromatography systems can provide high-resolution re-purification results.

An Effective QWBA/UHPLC-MS/Tissue Punch Approach: Solving a Pharmacokinetic Issue via Quantitative Met-ID.

Background: Methods to provide absolute quantitation of the administered drug and corresponding metabolites in tissue in a spatially resolved manner is a challenging but much needed capability in pharmaceutical research. Quantitative Whole-Body Autoradiography (QWBA) after a single- dose intravenous (3 mg/kg) and extravascular (30 mg/kg) administrations of an in vitro metabolically stable test compound (structure not reported here) indicated quick tissue distribution and excretion.

Objective: Good bioavailability and short in vivo half-lives were determined formerly for the same test compound.

Isolation, Co-Crystallization and Structure-Based Characterization of Anabaenopeptins as Highly Potent Inhibitors of Activated Thrombin Activatable Fibrinolysis Inhibitor (TAFIa).

Mature thrombin activatable fibrinolysis inhibitor (TAFIa) is a carboxypeptidase that stabilizes fibrin clots by removing C-terminal arginines and lysines from partially degraded fibrin. Inhibition of TAFIa stimulates the degradation of fibrin clots and may help to prevent thrombosis. Applying a lead finding approach based on literature-mining, we discovered that anabaenopeptins, cyclic peptides produced by cyanobacteria, were potent inhibitors of TAFIa with IC50 values as low as 1.

Biosynthetic Studies of Telomycin Reveal New Lipopeptides with Enhanced Activity.

Telomycin (TEM) is a cyclic depsipeptide antibiotic active against Gram-positive bacteria. In this study, five new natural telomycin analogues produced by Streptomyces canus ATCC 12646 were identified. To understand the biosynthetic machinery of telomycin and to generate more analogues by pathway engineering, the TEM biosynthesis gene cluster has been characterized from S.