11/14/2024


It was shown exemplarily with one representative ligand from the series that such berberine-adenine conjugates exhibit a selective binding, specifically a selectivity to quadruplex DNA in competition with duplex DNA, and a preferential thermal stabilization of the G4-DNA forms 22AG and KRAS. Notably, the experimental data do not provide evidence for a significant effect of the adenine unit on the binding affinity of the ligands, for example, by additional association with the loops, presumably because the adenine residue is sterically shielded by the neighboring triazole unit.In this paper we describe the synthesis of a new carbohydrate-based building block functionalized with azido or amino groups on the 2 and 4 positions. The building block can be synthesized in anomerically pure form in only five scalable steps starting from commercially available levoglucosan. It was shown that the building block could undergo alkylations under strongly basic conditions. The building block with azido groups could furthermore take part in CuAAC reactions, generating derivatives with ester or carboxylic acid functionalities. In addition, the anomeric mixture of the building block was used for the synthesis of a molecule that could act as an emulsifier only in the presence of Zn2+ ions.Male ithomiine butterflies (Nymphalidae Danainae) have hairpencils on the forewings (i.e., androconia) that disseminate semiochemicals during courtship. While most ithomiines are known to contain derivatives of pyrrolizidine alkaloids, dihydropyrrolizines, or γ-lactones in these androconia, here we report on a new class of fatty acid esters identified in two subspecies, Ithomia salapia aquinia and I. s. derasa. The major components were identified as isoprenyl (3-methyl-3-butenyl) (Z)-3-acetoxy-11-octadecenoate, isoprenyl (Z)-3-acetoxy-13-octadecenoate (12) and isoprenyl 3-acetoxyoctadecanoate (11) by GC/MS and GC/IR analyses, microderivatizations, and synthesis of representative compounds. The absolute configuration of 12 was determined to be R. The two subspecies differed not only in the composition of the ester bouquet, but also in the composition of more volatile androconial constituents. While some individuals of I. s. aquinia contained ithomiolide A (3), a pyrrolizidine alkaloid derived γ-lactone, I. s. derasa carried the sesquiterpene α-elemol (8) in the androconia. These differences might be important for the reproductive isolation of the two subspecies, in line with previously reported low gene exchange between the two species in regions where they co-occur. Furthermore, the occurrence of positional isomers of unsaturated fatty acid derivatives indicates activity of two different desaturases within these butterflies, Δ9 and Δ11, which has not been reported before in male Lepidoptera.Between 16 May and 15 August 2020, seven highly pathogenic avian influenza (HPAI) A(H5N8) virus outbreaks were reported in Europe in poultry, with one outbreak reported in Bulgaria(n=1) andsix in Hungary (n=6) and one low pathogenic avian influenza (LPAI) A(H5N3) virus outbreak was reported in poultry in Italy. All six outbreaks detected in Hungary were secondary outbreaks and seem to be the tail end of the HPAI A(H5N8) epidemic that wasobserved in poultry over the winter and spring in central Europe from December 2019 (n=334).Genetic analysis of the HPAI A(H5N8) viruses isolated during this reporting period from Bulgaria and Hungary did not identify any major changes compared tothe viruses collected in the respective countries during the first months of 2020. This suggests a persistence of the virus in the two countries rather than new introductions via infectedwild birds. HPAI A(H5N8) virus has been detected in poultry and wild birds in western Russia within the reporting period, and as of the middle of September also in Kazakhstan. The presence of HPAI virus in western Russiaand in north Kazakhstan,spatially associated with autumnmigration routes of wild waterbirds, is of concern due to the possible spread of the virus via wild birds migrating to the EU.It is highly recommended thatMember States take appropriate measures to promptly detect suspected cases of HPAI, including increasing biosecurity measures. According to past experiences (2005-2006 and 2016-2017 epidemic waves), the northern and eastern European areas might be at higher risk of virus introduction in the coming autumn-winter seasonand should be the key regions where prompt response measures to early detect the virusshould be set up. One human case due to A(H9N2) avian influenza virus infection was reported during the reporting period.Since 16 October 2020, outbreaks ofhighly pathogenic avian influenza (HPAI) viruseshavebeen reported inseveral EU/EEAcountries -Belgium, Denmark, France, Germany, Ireland, the Netherlands, and Swedenas well asin the United Kingdom.As of 19 November,12pm, 302 HPAI A(H5) detections have been reported, with the majority of the detections referring to wild birds (n=281), and a few related to outbreaks in poultry (n=18) and captive birds (n=3). https://www.selleckchem.com/products/gsk-3008348-hydrochloride.html Most of the detections in wild birds were in wild waterbirds,being barnacle goose the most affected species (n=110), followed by greylag goose (n=47), Eurasian wigeon (n=32),mallard (n=14), and common buzzard (n=13).ThreeHPAI virus subtypes were identified, A(H5N8), A(H5N5) and A(H5N1), with A(H5N8) being the most reported subtype (n=284). Phylogenetic analysis indicated that the viruses evolved from a single progenitor virus thatwent through multiple reassortment events. Based on the ongoing autumn migration of wild waterbirds to their wintering areas in Europe, there is a continued risk of further introduction of HPAI A(H5) viruses into Europe. Furthermore, given the expected movements of both migratory, and resident wild birds in Europe during winter, there is a high risk of further spread of HPAI A(H5) viruses within Europe. No genetic markers indicating adaptation to mammals have been identified in the viruses analysed so far,andno human infection due to avian influenza viruses detected in the recent outbreakshas been reported. For that reason,the risk to the general population remains very low.However,following the precautionary principle, people should avoid touching sick or dead birds unprotected to minimise any potential risk.