success-story

Bacterial secondary metabolites display diverse biological activities, thus having potential as pharmacological agents. Although most of these compounds are discovered by random screening, it is possible to predict and re-design their structures based on the information on their biosynthetic pathways. Biosynthesis of macrolides, governed by modular polyketide synthases (PKS), obeys certain rules, which can be […]

applicability for this approach.

Familial amyotrophic lateral sclerosis (FALS) is a fatal motor neuron disease that is caused by mutations in the gene encoding superoxide dismutase-type 1 (SOD1). The affected regions of the FALS brain are characterized by aggregated SOD1, and the mutations that destabilize SOD1 appear to promote its aggregation in vitro. Because dissociation of the native SOD1 […]

With the annotation of the human genome approaching completion, public-sector researchers – spurred in part by various National Institutes of Health Roadmap Initiatives – have become increasingly engaged in drug discovery and development efforts. Although large and diverse chemical libraries of ‘drug-like’ compounds can be readily screened to yield chemically novel scaffolds, transforming these ‘chemical […]

Nystatin is an antifungal compound with potent proinflammatory properties. Herein, we demonstrate that nystatin induces interleukin (IL)-1beta, IL-8, and tumor necrosis factor alpha secretion through its activation of toll-like receptor 1 (TLR1) and TLR2. Hence, a TLR-dependent mechanism could serve as the molecular basis for the proinflammatory properties of nystatin.

Family 18 chitinases play key roles in a range of pathogenic organisms and are overexpressed in the asthmatic lung. By screening a library of marketed drug molecules, we have identified methylxanthine derivatives as possible inhibitor leads. These derivatives, theophylline, caffeine, and pentoxifylline, are used therapeutically as antiinflammatory agents, with pleiotropic mechanisms of action. Here it […]

Introduction: Direct block of IKr by non-antiarrhythmic drugs (NARDs) is a major cause of QT prolongation and torsades de pointes (TdP), and has made the hERG potassium channel a major target of drug safety programs in cardiotoxicity. Block of hERG currents is not the only way that drugs can adversely impact the repolarizing current IKr, […]

Tissue transglutaminase (TGase) is a Ca2+-dependent enzyme that catalyzes cross-linking of intracellular proteins through a mechanism that involves isopeptide bond formation between Gln and Lys residues. In addition to its transamidation activity, TGase can bind guanosine 5???-triphosphate (GTP) and does so in a manner that is antagonized by calcium. Once bound, GTP undergoes hydrolysis to […]

The invention relates to a bath for the electrodeposition of gold and gold alloys and to its use for producing dental moldings. In this bath, the gold is in the form of a gold sul?te complex. The bath according to the invention and/or the use according to the invention is distinguished by the fact that […]