Synthetic bulky NS4A peptide variants bind to and inhibit HCV NS3 protease.

NS4A is a non-structural multi-tasking small peptide that is essential for HCV maturation and replication. The central odd-numbered hydrophobic residues of NS4A (Val-23' to Leu-31') are essential for activating NS3 upon NS3/4A protease complex formation. This study aims to design new specific allosteric NS3/4A protease inhibitors by mutating Val-23', Ile-25', and Ile-29' into bulkier amino acids.

1-Imidazole-2,5-Dicarboxamides as NS4A Peptidomimetics: Identification of a New Approach to Inhibit HCV-NS3 Protease.

The nonstructural (NS) protein NS3/4A protease is a critical factor for hepatitis C virus (HCV) maturation that requires activation by NS4A. Synthetic peptide mutants of NS4A were found to inhibit NS3 function. The bridging from peptide inhibitors to heterocyclic peptidomimetics of NS4A has not been considered in the literature and, therefore, we decided to explore this strategy for developing a new class of NS3 inhibitors.

Aryloxyalkanoic Acids as Non-Covalent Modifiers of the Allosteric Properties of Hemoglobin.

Hemoglobin (Hb) modifiers that stereospecifically inhibit sickle hemoglobin polymer formation and/or allosterically increase Hb affinity for oxygen have been shown to prevent the primary pathophysiology of sickle cell disease (SCD), specifically, Hb polymerization and red blood cell sickling. Several such compounds are currently being clinically studied for the treatment of SCD. Based on the previously reported non-covalent Hb binding characteristics of substituted aryloxyalkanoic acids that exhibited antisickling properties, we designed, synthesized and evaluated 18 new compounds (KAUS II series) for enhanced antisickling activities.

Analysis of abiraterone stress degradation behavior using liquid chromatography coupled to ultraviolet detection and electrospray ionization mass spectrometry.

A validated stability-indicating LC-UV-ESI-MS analytical method was established to analyze abiraterone (ABR) and its potential degradation products (DPs) and was performed according to ICH guidelines. Trace amounts of DPs that might be released under different environmental conditions were determined. Stress conditions, including the effect of heat, acid-base hydrolysis, oxidation and UV-light were investigated.

Brominated arginine-derived alkaloids from the red sea sponge Suberea mollis.

Investigation of a new collection of the Red Sea sponge Suberea mollis afforded two new brominated arginine-derived alkaloids, subereamines A (1) and B (2), a new brominated phenolic compound, subereaphenol D (3), and the known compounds dichloroverongiaquinol (4), aerothionin (5), and purealdin L (6). The structures of the isolated compounds were assigned using one- and two-dimensional NMR spectra and HRFABMS data. The absolute configurations of subereamines A (1) and B (2) were determined by acid hydrolysis followed by chiral-phase LC-MS.