Chemical constituents of Stereum subtomentosum and two other birch-associated basidiomycetes: an interspecies comparative study.

Metabolites of the wood-rotting fungus Stereum subtomentosum Pouzar (Basidiomycetes, order Russulales, family Stereaceae) occurring on birch (Betula pendula Roth) trees were phytochemically investigated for the first time. Three main metabolite chemotypes present in MeOH extracts of the fruit bodies, viz. steroids, fatty acids, and water-soluble sugars, were fractionated, isolated, and identified by 1D/2D NMR-spectroscopic analyses, NMR data comparisons, and chemical correlations combined with GC/MS experiments.

The anticancer drug ellipticine forms covalent DNA adducts, mediated by human cytochromes P450, through metabolism to 13-hydroxyellipticine and ellipticine N2-oxide.

Ellipticine is an antineoplastic agent, the mode of action of which is considered to be based on DNA intercalation and inhibition of topoisomerase II. We found that ellipticine also forms the cytochrome P450 (CYP)-mediated covalent DNA adducts. We now identified the ellipticine metabolites formed by human CYPs and elucidated the metabolites responsible for DNA binding.

An nmr conformational analysis of a synthetic peptide Cn2(1-15)NH2-S-S-acetyl-Cn2(52-66)NH2 from the New World Centruroides noxius 2 (Cn2) scorpion toxin: comparison of the structure with those of the Centruroides scorpion toxins.

The solution structure of a synthetic peptide, Cn2(1-15)NH2-S-S-acetyl-Cn2(52-66)NH2 from toxin 2 (Cn2) of the New World scorpion Centruroides noxius was determined using nmr and molecular dynamics calculations. The peptide has no significant secondary structure such as an alpha-helix or a beta-sheet, yet it has a fixed conformation for the first chain. The backbone secondary structure involving residues 6-12 in this peptide shows an excellent overlap with the structures of natural neurotoxins from Centruroides sculpturatus Ewing.

A comparative NMR and molecular dynamics study of the conformations of bradykinin B1 and B2, B2, and B1-specific receptor antagonists B-9430, B-9436, and B-9858.

Extensive proton magnetic resonance experiments were carried out on three bradykinin peptide antagonists B-9430, B-9436, and B-9858 in aqueous solutions as well as in sodium dodecylsulphate micelles (B-9430 and B-9436) and CD3OH/H2O (60%/40%) mixtures for B-9858. All three peptides showed no observable secondary structure in aqueous solution. However, in their respective structure-inducing solvents, B-9430 (B1 and B2 receptor antagonist) and B-9436 (a B2 receptor antagonist) exhibit a type II beta-turn involving residues 2-5, and B-9430 also exhibits a type II' beta-turn involving residues 6-9 (in sodium dodecylsulfate micellar solutions), whereas B-9858, a B1-specific receptor antagonist, exhibits only a type II beta-turn involving residues 2-5 (in CD3OH/H2O solutions).

An NMR, CD, molecular dynamics, and fluorometric study of the conformation of the bradykinin antagonist B-9340 in water and in aqueous micellar solutions.

A detailed NMR, CD, fluorometry, and molecular modeling study of a novel bradykinin antagonist B-9340, containing a novel amino acid D-Igl (alpha-(2-indanyl)glycine) at position 7, was carried out. The sequence of B-9340 is D-Arg0-Arg1-Pro2-Hyp3-Gly4-Thi5-Ser6-D- Igl7-Oic8-Arg9, where Hyp is hydroxyproline, Thi is beta-(2-thienyl)alanine, and Oic is (3aS,7aS)-octahydroindole-2-carboxylic acid. The CD results exhibit a striking effect of SDS on the spectrum of the BK antagonist, indicating that interaction with the surfactant induces a folded peptide structure.

Structurally defined synthetic cancer vaccines: analysis of structure, glycosylation and recognition of cancer associated mucin, MUC-1 derived peptides.

Translation of an immune response into therapy is probably the toughest task in designing vaccines for cancer due to the heterogeneity of the cell surface antigens which display tremendous variations in glycoforms. Consequently, a small segment (antigen) of cancer-associated mucin, in spite of generating antigen-specific immune responses, may be limited in therapeutic value. It is important that the synthetic segment resembles the native cancer-associated mucin in both structure and conformation.

Flavovirin--a new antifungal antibiotic produced by the pyrenomycete Melanconis flavovirens.

The pyrenomycete Melanconis flavovirens was found to produce a mixture of two antifungal antibiotics. The first has been already described; the antibiotic is identical with thermozymocidin (myriocin). The second antibiotic is a new compound, whose isolation and identification is presented in this paper.