Crystal structure of a squalene cyclase in complex with the potential anticholesteremic drug Ro48-8071

Squalene-hopene cyclase (SHC) catalyzes the conversion of squalene into pentacyclic compounds. It is the prokaryotic counterpart of the eukaryotic oxidosqualene cyclase (OSC) that catalyzes the steroid scaffold formation. Because of clear sequence homology, SHC can serve as a model for OSC, which is an attractive target for anticholesteremic drugs. We have established the crystal structure of SHC complexed with Ro48-8071, a potent inhibitor of OSC and therefore of cholesterol biosynthesis. Ro48-8071 is bound in the active-center cavity of SHC and extends into the channel that connects the cavity with the membrane. The binding site of Ro48-8071 is largely identical with the expected site of squalene; it differs from a previous model based on photoaffinity labeling. The knowledge of the inhibitor binding mode in SHC is likely to help develop more potent inhibitors for OSC.     

Excitation of analytes and enhancement of emission intensities in a d.c. plasma jet: a critical review leading to proposed mechanistic models

Experimental data and theoretical criteria are used to critically review existing models for analyte emission enhancement in the 3-electrode d.c. plasma (DCP). The analytical zone is characterized as a non-optically thin recombining plasma in partial thermodynamic equilibrium (PTE). Spectrochemical excitation the authors ascribe largely to: (1) argon resonance line radiative transport; (2) inversion of optically pumped argon states; (3) inversion of analyte populations by Franck-Condon collisions with argon; (4) energy cascading in analytes via a multitude of channels. Adding an easily ionized element (EIE): (1) induces additional resonance line radiative transfer; (2) raises electron densities in cooler, analyte-rich plasma margins; (3) locally increases argon optical absorption cross sections via Stark broadening; (4) redistributes ohmic heating. Coupling between the proposed mechanisms is non-linear. Relationships between radiative transfer and collisional redistribution and (1) background suppression by EIE and (2) analyte emission enhancement by helium are also examined. Similarities between DCP and inductively coupled plasma (ICP) excitation mechanisms are noted and practical implications are addressed.     

Ansamycine, 1. Mitt.: Chemie der Metacycloprodigiosine,Synthese des [9](2,4)Pyrrolophans

Some syntheses of [9](2,4)pyrrolophane are described.     

Synthese ab-trans-anellierter derivate des tricyclischen diterpens pleuromutilin durch intramolekulare 1,5-hydrid-verschiebung

The Diterpene Pleuromutilin(1) reacts with orthoformicacid-trimethylester at room temperature almost quantitatively to give the 11-keto-3-methylester 2 with AB-trans-configuration. This conversion is shown to occur through a 1,5-hydride-shift between C3 and C11. Treatment of 2 with Lewis acid (ZnCl₂) initiated a retro-1,5-hydride-shift which resulted in the formation of Pleuromutilin(1). Mechanistic aspects and structure assignments, which are based on chemical and spectroscopic (¹H- and ¹³C-NMR) data are discussed.