New Sesquiterpenes from Aspergillus terreus Thom

Four neutral sesquiterpenes were isolated from the culture filtrate of of Aspergillus terreus THOM NO. 14 which produces two sesquiterpene antibiotics, terrecyclic acid A and terrecyclol. On the basis of spectroscopic data the structures of four neutral sesquiterpenes were elucidated. One of these is quadrone, a known antitumor substance, but isoquadrone, 8-hydroxyquadrone and 6-hydroxyisoquadrone are new sesquiterpenes. Although terrecyclic acid A exhibits antimicrobial and antitumor activities, these four scarcely show these activities.     

DNA conformation of the region preceding the beta-lactamase promoter of pUC19 which is required for efficient transcription.

The upstream region of the beta-lactamase promoter of Escherichia coli plasmid pUC19 has a DNA curvature (bent DNA). This region was replaced with another sequence by using randomly synthesized oligonucleotides. Among the reconstructed plasmids, a plasmid which could endow E. coli cells with the strongest resistance to ampicillin on plates was selected. Nucleotide sequence and DNA conformation of the altered region was investigated.     

Isolation and Biological Activity of Cyl-2, a Metabolite of Cylindrocladium scoparium

Three metabolites designated Cyl–1, –2 and –3 were isolated as plant growth regulators from culture filtrate of Cylindrocladium scoparium Morgan, a phytopathogenic fungus. Cy1–2 was obtained as pure crystals, and it revealed marked inhibitory activity on the root growth of lettuce seedlings. Cyl–1 showed inhibition on the same organ, while Cyl–3 showed promotion.     

Kinetochore stretching-mediated rapid silencing of the spindle-assembly checkpoint required for failsafe chromosome segregation

1. Download : Download high-res image (152KB)
2. Download : Download full-size image

     

Flexibility of small molecular CD4 mimics as HIV entry inhibitors

CD4 mimics such as YIR-821 and its derivatives are small molecules which inhibit the interaction between the Phe43 cavity of HIV-1 gp120 with host CD4, an interaction that is involved in the entry of HIV to cells. Known CD4 mimics generally possess three structural features, an aromatic ring, an oxalamide linker and a piperidine moiety. We have shown previously that introduction of a cyclohexyl group and a guanidine group into the piperidine moiety and a fluorine atom at the meta-position of the aromatic ring leads to a significant increase in the anti-HIV activity. In the current study, the effects of conformational flexibility were investigated by introduction of an indole-type group in the junction between the oxalamide linker and the aromatic moiety or by replacement of the oxalamide linker with a glycine linker. This led to the development of compounds with high anti-HIV activity, showing the importance of the junction region for the expression of high anti-HIV activity. The present data are expected to be useful in the future design of novel CD4 mimic molecules.     

Proteinaceous factor(s) in culture supernatant fluids of bifidobacteria which prevents the binding of enterotoxigenic Escherichia coli to gangliotetraosylceramide.

We have examined the competitive binding of several species of Bifidobacterium and Escherichia coli Pb176, an enterotoxigenic E. coli (ETEC) strain, to gangliotetraosylceramide (asialo GM1 or GA1), a common bacterium-binding structure, and identified a factor(s) in the Bifidobacterium culture supernatant fluid that inhibits the binding of E. coli Pb176 to GA1. The ETEC strain we used expresses colonization factor antigen (CFA) II, which consists of coli surface-associated antigens CS1 and CS3. Competitive exclusion of ETEC from GA1 molecules by Bifidobacterium cells was found by an in vitro thin-layer chromatography overlay binding suppression assay. However, the ETEC cells were less effective in blocking the adherence of Bifidobacterium cells to GA1. These findings suggest that the two bacterial species recognize different binding sites on the GA1 molecule and that the mechanism of competitive exclusion is not due to specific blockage of a common binding site on the molecule. The neutralized culture supernatant fluids of Bifidobacterium species, including that of Bifidobacterium longum SBT 2928 (BL2928), showed remarkable inhibition of the ETEC binding to GA1. Our results suggest that the binding inhibitor produced by BL2928 is a proteinaceous molecule(s) with a molecular weight around or over 100,000 and a neutral isoelectric point. The binding inhibitor produced by BL2928 and other Bifidobacterium species is estimated to contribute to their normal anti-infectious activities by preventing the binding of pathogenic strains of E. coli to GA1 on the surface of the human intestinal mucosa.     

Suppression of electrophoretic anomaly of bent DNA segments by the structural property that causes rapid migration.

Intrinsic DNA curvature is speculated to be a common feature of all satellite DNA sequences and may aid in the tight winding of DNA in constitutive heterochromatin. Several satellite DNAs, however, show unusually rapid migration in non-denaturing polyacrylamide gels, which is just the opposite behavior of that shown by curved DNA structures. Employing bovine satellite I DNA monomer, we attempted to understand the molecular mechanism of 'rapid migration'. The phenomenon of rapid migration was temperature-dependent and to a small extent polyacrylamide-concentration-dependent. Physiological or near-physiological concentrations of Mg2+and Ca2+ions bent the rapid migrating DNA segment. Predominance of purine-purine base stacking over purine-pyrimidine in nucleotide sequence was strongly indicated to be the cause of the rapid migration. Furthermore, they seemed to be implicated in the formation of induced DNA bend. We also found that the satellite I monomer contains an intrinsic DNA curvature as do many other satellites. Heretofore, the rapid migration property has concealed the presence of curvature.