Identification of lignans and related compounds in Anthriscus sylvestris by LC-ESI-MS/MS and LC-SPE-NMR.

The aryltetralin lignan deoxypodophyllotoxin is much more widespread in the plant kingdom than podophyllotoxin. The latter serves as a starting compound for the production of cytostatic drugs like etoposide. A better insight into the occurrence of deoxypodophyllotoxin combined with detailed knowledge of its biosynthestic pathway(s) may help to develop alternative sources for podophyllotoxin.

Ligand-based NMR spectra demonstrate an additional phytoestrogen binding site for 17beta-hydroxysteroid dehydrogenase type 1.

The enzyme 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) has become an important drug target for breast cancer because it catalyzes the interconversion of estrone to the biologically more potent estradiol which also plays a crucial role in the etiology of breast cancer. Patients with an increased expression of the 17beta-HSD1 gene have a significantly worse outcome than patients without. Inhibitors for 17beta-HSD1 are therefore included in therapy development.

SALMON: solvent accessibility, ligand binding, and mapping of ligand orientation by NMR spectroscopy.

Quinone oxidoreductase 2 (NQO2) binds the prodrug tretazicar (also known as CB1954, 5-(aziridin-1-yl)-2,4-dinitrobenzamide), which exhibits a profound antitumor effect in human cancers when administered together with caricotamide. X-ray structure determination allowed for two possible orientations of the ligand. Here we describe a new NMR method, SALMON (solvent accessibility, ligand binding, and mapping of ligand orientation by NMR spectroscopy), based on waterLOGSY to determine the orientation of a ligand bound to a protein by mapping its solvent accessibility, which was used to unambiguously determine the orientation of CB1954 in NQO2.

Surface plasmon resonance evaluation of various aminoglycoside-RNA hairpin interactions reveals low degree of selectivity.

Aminoglycoside antibiotics, which are able to selectively bind to RNA, are considered to be an important lead in RNA-targeting drug discovery. In this study, surface plasmon resonance (SPR) was employed to explore the interaction of aminoglycosides with known tobramycin-binding RNA hairpins (aptamers) and an unrelated RNA hairpin. It was established that aminoglycosides have multiple interactions with RNA hairpins.

Targeting RNA: new opportunities to address drugless targets.

Historically, pharmaceutical industries have focussed on the discovery of compounds that target the protein products of genes. The intermediary product between gene and protein, consisting of RNA, has remained largely unexplored. Several drugs targeting the rRNA of bacteria have been, however, in clinical use for over half a century.