1-Norbornyllithium as a Precursor for the Synthesis of Novel Organic 1-Bicyclo[2.2.1]Heptane Derivatives and for the Improved Preparation of 1-Chloro-Bicyclo[2.2.2]octane

An improved strategy for synthesis of 1-chloro-bicyclo[2.2.2]octane is described in which the key compounds 1-norborny substituted ethyl formate(3) or 1-norbornylcarbaldehyde (7) were prepared from 1-norbornyllithium(1). The latter appeared as a useful precursor for the synthesis of various organic bridgehead substituted derivatives.     

Stahl und Eisen

Ohne Zusammenfassung     

Synthese von Tetradecano-14-lacton durch Ringerweiterung

Synthesis of Tetradecano-14-lactone by Ring Enlargement The aldehyde 3 , prepared by ozonolysis of 2-allyl-2-nitrocyclododecanone, gave the ring-enlargement product 5 (85%) by treatment with (i-Bu)₂AlH. Its transformation to the tetradecano-14-lactone ( 8 ) via the aldol ester 6 and other routes (best is reduction with Bu₃SnH, AlBN, toluene) was difficult. Remarkable is the smooth denitrification of 3 (loss of HNO₂) to the conjugated dione 4 by chromatography on silica gel or base treatment.     

Analysis of HIV-1 fusion peptide inhibition by synthetic peptides from E1 protein of GB virus C

The aim of this study was to identify proteins that could inhibit the activity of the peptide sequence representing the N-terminal of the surface protein gp41 of HIV, corresponding to the fusion peptide of the virus (HIV-1 FP). To do this we synthesized and studied 58 peptides corresponding to the envelope protein E1 of the hepatitis G virus (GBV-C). Five of the E1 synthetic peptides: NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10), QAGLAVRPGKSAAQLVGE (P18) and AQLVGELGSLYGPLSVSA (P22) were capable of inhibiting the leakage of vesicular contents caused by HIV-1 FP. A series of experiments were carried out to determine how these E1 peptides interact with HIV-1 FP. Our studies analyzed the interactions with and without the presence of lipid membranes. Isothermal titration calorimetry revealed that the binding of P7, P18 and P22 peptides to HIV-1 FP is strongly endothermic, and that binding is entropy-driven. Gibbs energy for the process indicates a spontaneous binding between E1 peptides and HIV-1 FP. Moreover, confocal microscopy of Giant Unilamellar Vesicles revealed that the disruption of the lipid bilayer by HIV-1 FP alone was inhibited by the presence of any of the five selected peptides. Our results highlight that these E1 synthetic peptides could be involved in preventing the entry of HIV-1 by binding to the HIV-1 FP. Therefore, the continued study into the interaction between GBV-C peptides and HIV-1 FP could lead to the development of new therapeutic agents for the treatment of AIDS.     

Interactions of membrane active peptides with planar supported bilayers: an impedance spectroscopy study

Membrane active peptides exert their biological effects by interacting directly with a cell's lipid bilayer membrane. These therapeutically promising peptides have demonstrated a variety of activities including antimicrobial, cytolytic, membrane translocating, and cell penetrating activities. Here, we use electrochemical impedance spectroscopy (EIS) on polymer-cushioned supported lipid bilayers constructed on single crystal silicon to study two pairs of closely related membrane active peptides selected from rationally designed, combinatorial libraries to have different activities in lipid bilayers: translocation, permeabilization, or no activity. Using EIS, we observed that binding of a membrane translocating peptide to the lipid bilayer resulted in a small decrease in membrane resistance followed by a recovery back to the original value. The recovery may be directly attributable to peptide translocation. A nontranslocating peptide did not decrease the resistance. The other pair, two membrane permeabilizing peptides, caused an exponential decrease of membrane resistance in a concentration-dependent manner. This permeabilization of the supported bilayer occurs at peptide to lipid ratios as much as 1000-fold lower than that needed to observe effects in vesicle leakage assays and gives new insights into the fundamental peptide-bilayer interactions involved in membrane permeabilization.     

The Guanidinium Group as a Key Part of Water‐Soluble Polymer Carriers for siRNA Complexation and Protection against Degradation

Here, the preparation of a novel block copolymer consisting of a statistical copolymer N‐(2‐hydroxypropyl) methacrylamide‐s‐N‐(3‐aminopropyl) methacrylamide and a short terminal 3‐guanidinopropyl methacrylamide block is reported. This polymer structure forms neutral but water‐soluble nanosized complexes with siRNA. The siRNA block copolymer complexes are first analyzed using agarose gel electrophoresis and their size is determined with fluorescence correlation spectroscopy. The protective properties of the polymer against RNA degradation are investigated by treating the siRNA block copolymer complexes with RNase V1. Heparin competition assays confirm the efficient release of the cargo in vitro. In addition, the utilization of microscale thermophoresis is demonstrated for the determination of the binding strength between a fluorescently labeled polyanion and a polymer molecule.

     

Multivariate statistical study of simultaneously monitored cloud water, aerosol and rainwater data from different elevation levels in an Alpine valley (Achenkirch, Tyrol, Austria)

The present paper deals with data interpretation of monitoring of various atmospheric events (cloud water, aerosol and rainwater) at three different elevation levels at Achenkirch profile in an Alpine valley, Tyrol, Austria (Christlumkopf-1758 m, Christlumalm-1280 m and Talboden-930 m a.s.l.) by the use of principal components analysis. From October 1995 to September 1996 sampling sessions for all sites from the profile and for all events were performed for the major ions NH₄⁺, Na⁺, K⁺, Ca²⁺, Mg²⁺, Cl⁻, NO₃⁻, SO₄²⁻-44 cases with eight variables for rainwater; 117 cases with eight variables for cloud water samples and 50 cases with seven variables for aerosol (the major ions as in rain- and cloud water but without magnesium) at any of the elevations. The aim of the multivariate statistical treatment was to extract information about latent factors determining the data structure in all of the cases in order to compare and interpret similarities and dissimilarities with respect to the elevation or the type of the atmospheric event. Four latent factors seem to explain over 85% of the total variance for almost all sites and events but the factors have different identification for the different events or sites (e.g. ‘anthropogenic’, ‘crustal’, ‘neutralization’, ‘salt’). Thus, a comparison between sites and between events becomes possible. It was found that cloud water and aerosol events are much more similar with respect to data structure (relevant to emission sources or processes of formation) than the same events and rainwater. Further, the upper sites of the profile (Christlumkopf and Christlumalm) also reveal data structure similarity differing from that of the lowest site Talboden.     

Structures of Ring-Enlargement Products

Crystal structures have been determined of methyl trans-1-hydroxy-6-nitro-3-oxobicyclo[4.4.0]decane-2-carboxylate ( 19 ), cis-3-methyl-6-nitro-2-oxabicyclo[4.4.0]decan-1-ol ( 2 ), cis-7-hydroxy-1-nitrobicyclo[5.4.0]undecan-9-one ( 13 ), and the medium-ring compounds 2-acetyl-4-nitrocyclooctanone ( 9 ), methyl 5-nitro-2-oxocyclooctane-carboxylate ( 4 ), 2-acetyl-4-nitrocyclononanone ( 11 ), 2-acetyl-4-nitrocyclodecanone ( 15 ), benzyl 5-nitro-2,11-dioxocycloundecanecarboxylate ( 24 ), methyl 5-nitro-2,12-dioxocyclododecanecarboxylate ( 21 ), and 8-nitro-11-oxo-13-tridecanolide ( 7 ), which are intermediates, side products, or end products of the ‘Zip’ ring-enlargement reaction. The conformations of most of the medium-ring compounds are very similar to equal-sized ring compounds previously determine by other authors.