Synthesis, Binding and Bioactivity of [gamma]-Methylene [gamma]-Lactam Ecdysone Receptor Ligands: Advantages of QSAR Models for Flexible Receptors

Nuclear hormone receptors, such as the ecdysone receptor, often display a large amount of induced fit to ligands. The size and shape of the binding pocket in the EcR subunit changes markedly on ligand binding, making modelling methods such as docking extremely challenging. It is, however, possible to generate excellent 3D QSAR models for a given type of ligand, suggesting that the receptor adopts a relatively restricted number of binding site configurations or [`]attractors'. We describe the synthesis, in vitro binding and selected in vivo toxicity data for [gamma]-methylene [gamma]-lactams, a new class of high-affinity ligands for ecdysone receptors from Bovicola ovis (Phthiraptera) and Lucilia cuprina (Diptera). The results of a 3D QSAR study of the binding of methylene lactams to recombinant ecdysone receptor protein suggest that this class of ligands is indeed recognized by a single conformation of the EcR binding pocket.

The rα structure, chemical shift anisotropy, and the abnormal orientation of methyldichlorophosphine from the NMR spectrum

NMR studies of methyldichlorophosphine have been undertaken in the nematic phase of mixed liquid crystals of opposite diamagnetic anisotropies. The rα structure is derived. The proton chemical-shift anisotropy has been determined from the studies without the use of a reference compound and without a change of experimental conditions. It is shown that the molecule orients in the liquid crystal with positive diamagnetic anisotropy in such a way that the C3 symmetry axis of the CH3P moiety is preferentially aligned perpendicular to the direction of the magnetic field, unlike other similar systems. This is interpreted in terms of the formation of a weak solvent-solute molecular complex. The heteronuclear indirect spin-spin coupling constants are determined. The sign of the two-bond JPH is found to be positive.

Ilse Goldschmidt nee Molling with her sons Ernest and Frank Goldschhmidt on her 80th birthday; Laguna Hills, California.

Left to Right: Ernest Goldschmidt, Ilse Goldschmidt born Molling, and Frank Goldschmidt. The picture was taken on the occasion of Ilse's 80th birthday party 22 Dec 1989 Laguna Hills, CA.

High-resolution melt-curve analysis of random amplified polymorphic DNA (RAPD-HRM) for the characterisation of pathogenic leptospires: intra-serovar divergence, interserovar convergence, and evidence of attenuation in Leptospira reference collections.

High-resolution melt-curve analysis of random amplified polymorphic DNA (RAPD-HRM) is a novel technology that has emerged as a possible method to characterise leptospires to serovar level. RAPD-HRM has recently been used to measure intra-serovar convergence between strains of the same serovar as well as inter-serovar divergence between strains of different serovars. The results indicate that intra-serovar heterogeneity and inter-serovar homogeneity may limit the application of RAPD-HRM in routine diagnostics. They also indicate that genetic attenuation of aged, high-passage-number isolates could undermine the use of RAPD-HRM or any other molecular technology. Such genetic attenuation may account for a general decrease seen in titres of rabbit hyperimmune antibodies over time. Before RAPD-HRM can be further advanced as a routine diagnostic tool, strains more representative of the wild-type serovars of a given region need to be identified. Further, RAPD-HRM analysis of reference strains indicates that the routine renewal of reference collections, with new isolates, may be needed to maintain the genetic integrity of the collections.

Tombstone of David Benjamin; Strangriede Cemetery (R 84.7); Hannover Cemeteries Tombs

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Tombstone of H. Solomon; Strangriede Cemetery (R 83); Hannover Cemeteries Tombs

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Tombstone of Frederike Benjamin nee Salamon; Strangriede Cemetery (R 83); Hannover Cemeteries Tombs

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Tombstone of Herz Benjamin (Naftali); Strangriede Cemetery (R 83.12); Hannover Cemeteries Tombs

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Tombstone of Max Molling; Strangriede Cemetery (R 29.10); Hannover Cemeteries Tombs

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Tombstone of Marianne Benjamin nee Sussmann; Strangriede Cemetery (R 83.9); Hannover Cemeteries Tombs

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Tombstone of Arthur Molling; Strangriede Cemetery (R 26.05); Hannover Cemeteries Tombs

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Tombstones of Frederike Benjamin nee Salamon and her husband David Benjamin; Strangriede Cemetery (R 84.6 and R 84.7); Hannover Cemeteries; Tombs

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Tombstone of Jeanette Molling nee Benjamin; Strangriede Cemetery (R 26.06); Hannover Cemeteries Tombs

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Detail of tombstone of Arthur Molling; Strangriede Cemetery (R 26.05); Hannover Cemeteries Tombs

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Tombstones of Sophie Molling and Max Molling (center in shadow); Strangriede Cemetery (R 29.09 and R 29.10); Hannover Cemeteries Tombs

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