Discovery, isolation, heterologous expression and mode-of-action studies of the antibiotic polyketide tatiomicin from Amycolatopsis sp. DEM30355.

A genomic and bioactivity informed analysis of the metabolome of the extremophile Amycolatopsis sp. DEM30355 has allowed for the discovery and isolation of the polyketide antibiotic tatiomicin. Identification of the biosynthetic gene cluster was confirmed by heterologous expression in Streptomyces coelicolor M1152.

The Race for Hydroxamate-Based Zirconium-89 Chelators.

Metallic radionuclides conjugated to biological vectors via an appropriate chelator are employed in nuclear medicine for the diagnosis (imaging) and radiotherapy of diseases. For the application of radiolabeled antibodies using positron emission tomography (immunoPET), zirconium-89 has gained increasing interest over the last decades as its physical properties (t = 78.4 h, 22.

Head-to-head comparison of DFO* and DFO chelators: selection of the best candidate for clinical Zr-immuno-PET.

Purpose: Almost all radiolabellings of antibodies with Zr currently employ the hexadentate chelator desferrioxamine (DFO). However, DFO can lead to unwanted uptake of Zr in bones due to instability of the resulting metal complex. DFO*-NCS and the squaramide ester of DFO, DFOSq, are novel analogues that gave more stable Zr complexes than DFO in pilot experiments.

Radiolabelling of the octadentate chelators DFO* and oxoDFO* with zirconium-89 and gallium-68.

In recent years, clinical imaging with zirconium-89 (Zr)-labelled monoclonal antibodies (Ab) by positron emission tomography (immunoPET) has been gaining significant importance in nuclear medicine for the diagnosis of different types of cancer. For complexation of the radiometal Zr and its attachment to the Ab, chelating agents are required. To date, only the hexadentate chelator desferrioxamine (DFO) is applied in the clinic for this purpose.

Synthesis, Characterization, Cytotoxic Activity, and Metabolic Studies of Ruthenium(II) Polypyridyl Complexes Containing Flavonoid Ligands.

Four novel monocationic Ru(II) polypyridyl complexes were synthesized with the general formula [Ru(DIP)flv]X, where DIP is 4,7-diphenyl-1,10-phenanthroline, flv stands for the flavonoid ligand (5-hydroxyflavone in [Ru(DIP)(5-OHF)](PF), genistein in [Ru(DIP)(gen)](PF), chrysin in [Ru(DIP)(chr)](OTf), and morin in [Ru(DIP)(mor)](OTf)), and X is the counterion, PF, and OTf ̅ (triflate, CFSO̅), respectively. Following the chemical characterization of the complexes by H and C NMR, mass spectrometry, and elemental analysis, their cytotoxicity was tested against several cancer cell lines. The most promising complex, [Ru(DIP)(gen)](PF), was further investigated for its biological activity.

Traceless Cleavage of Protein-Biotin Conjugates under Biologically Compatible Conditions.

Biotinylation of amines is widely used to conjugate biomolecules, but either the resulting label is non-removable or its removal leaves a tag on the molecule of interest, thus affecting downstream processes. We present here a set of reagents (RevAmines) that allow traceless, reversible biotinylation under biologically compatible, mild conditions. Release following avidin-based capture is achieved through the cleavage of a (2-(alkylsulfonyl)ethyl) carbamate linker under mild conditions (200 mm ammonium bicarbonate, pH 8, 16-24 h, room temperature) that regenerates the unmodified amine.

An LC/MS/MS method for stable isotope dilution studies of β-carotene bioavailability, bioconversion, and vitamin A status in humans.

Isotope dilution is currently the most accurate technique in humans to determine vitamin A status and bioavailability/bioconversion of provitamin A carotenoids such as β-carotene. However, limits of MS detection, coupled with extensive isolation procedures, have hindered investigations of physiologically-relevant doses of stable isotopes in large intervention trials. Here, a sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) analytical method was developed to study the plasma response from coadministered oral doses of 2 mg [(13)C10]β-carotene and 1 mg [(13)C10]retinyl acetate in human subjects over a 2 week period.