The application of biomacromolecules to improve oral absorption by enhanced intestinal permeability: A mini-review

Infectious diseases are a major cause of morbidity and mortality worldwide, exacerbated by increasing antibiotic resistance in many bacterial species. The development of drugs with new modes of action is essential. A leading strategy is antivirulence, with the aim to target bacterial proteins that are important in disease causation and progression but do not affect growth, resulting in reduced selective pressure for resistance. Immunophilins, a superfamily of peptidyl-prolyl cis-trans isomerase (PPIase) enzymes have been shown to be important for virulence in a broad-spectrum of pathogenic bacteria. This Perspective will provide an overview of the recent advances made in understanding the role of each immunophilin family, cyclophilins, FK506 binding proteins (FKBPs), and parvulins in bacteria. Inhibitor design and medicinal chemistry strategies for development of novel drugs against bacterial FKBPs will be discussed. Furthermore, drugs against human cyclophilins and parvulins will be reviewed in their current indication as antiviral and anticancer therapies.

Targeting protein folding: A novel approach for the treatment of pathogenic bacteria

Discovery of pyrimidine nucleoside dual prodrugs and pyrazine nucleosides as novel anti-HCV agents

In the past few decades, magnetic resonance spectroscopy (MRS) and MR imaging (MRI) have developed into a powerful non-invasive tool for medical diagnostic and therapy. Especially 19F MR shows promising potential because of the properties of the fluorine atom and the negligible background signals in the MR spectra. The detection of temperature in a living organism is quite difficult and usually, external thermometers or fibers are used. Temperature determination via MRS needs temperature-sensitive contrast agents. This article reports first results of solvent and structural influences on the temperature sensitivity of 19F NMR signals of chosen molecules. By using this chemical shift sensitivity, a local temperature can be determined with a high precision. Based on this preliminary study, we synthesized five metal complexes and compared the results of all variable temperature measurements temperature. It is shown that the highest 19F MR signal temperature dependence is detectable for a fluorine nucleus in a Tm3+-complex.

19F VT NMR: Novel Tm3+ and Ce3+ Complexes Provide New Insight into Temperature Measurement Using Molecular Sensors.

Development of a cyclosporin A derivative with excellent anti-hepatitis C virus potency

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Development of a cyclosporin A derivative with excellent anti-hepatitis C virus potency