The nonapeptide leucinostatin A acts as a weak ionophore and as an immunosuppressant on T lymphocytes.

Earlier studies have disclosed that leucinostatin A, a hydrophobic nonapeptide antibiotic, assumes an alpha-helical secondary structure in nonpolar environments. The present report demonstrates that the peptide acts as a weak ionophore facilitating the transport of mono-and divalent cations through the plasma membrane of T lymphocytes and through artificial membranes. Leucinostatin A does not change the thymidine uptake of both resting mouse thymocytes and peripheral blood lymphocytes but dose-dependently prevents the activation of T lymphocytes by tetradecanoyl-phorbol-acetate and by anti-T cell receptor antibody.

Molecular dynamics through 2H spin-lattice relaxation time measurements with an enzyme-inhibitor complex: lysozyme and methyl N-acetyl glucosaminides.

Deuteron spin-lattice relaxation times of specifically labelled methyl N-acetyl-D-glucosaminides associated to lysozyme were measured from 1H and 2H NMR spectra through bandshape analysis and FT inversion-recovery technique, respectively. Model calculations were carried out in order to assess the limits of the extreme narrowing approximation for the systems studied. Rotational correlation times of the acetamido methyl groups were analyzed in terms of anisotropic overall reorientation combined with internal rotation. The acetamido methyl group undergoes fast internal rotation in the alpha-glycoside complex about an axis nearly parallel with the major ellipsodial axis of lysozyme. More rotational freedom is likely to occur in the beta-glycoside complex.

Microbial conversion of daunorubicin into N-acetyl-13(S)-dihydrodaunomycin and bisanhydro-13-dihydrodaunomycinone.

By using a strain of Streptomyces willmorii, daunorubicin (daunomycin) was stereoselectively converted into N-acetyl-13(S)-dihydrodaunomycin and bisanhydro-13-dihydrodaunomycinone. The absolute stereochemistry of the new chiral center in N-acetyl-13(S)-dihydrodaunomycin was established by means of nuclear Overhauser effect measured in the 9,13-O-isopropylidene derivative.

Griseochelin, a novel carboxylic acid antibiotic from Streptomyces griseus.

Griseochelin, C33H60O7, isolated from an asporogenous strain of Streptomyces griseus represents a novel carboxylic acid antibiotic. The metabolite, which is active against Gram-positive bacteria, forms water-insoluble salts with mono- and divalent cations and binds alkaline-earth metal ions specifically in 2:1 (X2M) stoichiometry. Detailed spectral (IR, MS and NMR) studies provide full characterization of its constitution featuring a carboxylic acid function, a substituted tetrahydropyran ring, an allylic OH group which are accommodated within a tetrahydroxylated-octamethyl-C25 diene backbone.

Isolation and structures of nitrogen-free platenolide glycosides. I. The 5-O-(deoxy-3'-C-acetyl-beta-D-hexopyranosyl)-platenolides I and II.

Four novel nitrogen-free glycosides of platenolides I and II were isolated as secondary shunt metabolites of the turimycin biosynthesis from the culture broth of an industrial strain of Streptomyces hygroscopicus IMET JA 6599. By spectral (MS, 1H and 13C NMR) studies the structures of the glycosides have been settled as 5-O-(4',6'-dideoxy-3'-C-acetyl-beta-D-hexopyranosyl)-platenolide I (DDAH-Pl-I), 5-O-(4',6'-dideoxy-3'-C-acetyl-beta-D-hexopyranosyl)-platenolide II (DDAH-Pl-II), 5-O-(4',6'-dideoxy-3'-C-acetyl-beta-D-hexopyranosyl)-14-hydroxyl-platenolide II (DDAH-OH-Pl-II) and 5-O-(6'-deoxy-3'-C-acetyl-beta-D-hexopyranosyl)-platenolide II (DAH-Pl-II). A fifth glycoside, 5-O-(6'-deoxy-3'-C-acetyl-beta-D-hexopyranosyl)-platenolide I (DAH-Pl-I) was identified through its MS data.

Isolation and structures of nitrogen-free platenolide glycosides. II. The 5-O-(alpha-mycarosyl)- and 5-O-(3'-demethyl-beta-mycaroxyl)-platenolides I and II.

Three novel glycosides of platenolides I and II containing either mycarose (2,6-dideoxy-3-C-methyl-L-ribohexopyranose) or 3-demethyl-mycarose (2,6-dideoxy-L-ribohexopyranose) were isolated as the shunt products of turimycin biosynthesis by an industrial strain of Streptomyces hygroscopicus IMET JA 6599. By means of MS, 13C and 1H NMR spectroscopic studies, their structures were assigned as 5-O-(alpha-mycarosyl)-platenolide I (MYC-Pl-I), 5-O-(alpha-mycarosyl)-platenolide II (MYC-Pl-II) and 5-O-(3'-demethyl-beta-mycarosyl)-platenolide II (DM-MYC-Pl-II). The occurrence of 3-demethyl-mycaroside amongst the shunt metabolites is discussed in terms of its biosynthesis.

Constitution and absolute stereochemistry of the antibiotic sarubicin A.

By spectral (UV-VIS, IR, NMR, MS and CD) methods the quinone antibiotics sarubicin A and U-58,431 were shown to have identical constitution and stereochemistry. Chiroptical data and their theoretical analysis have settled the common absolute configuration as 5S, 6R, 8R, 10R.

Conformations of proline-containing cyclic peptides. 1H and 13C n.m.r. evidence for a solvent stabilized All-Cis X-Pro conformer of Cyclo-(Pro-Gly-Gly-Pro)2.

As inferred from 13C, 1H n.m.r. data, CD measurements and ion-binding experiments, the title molecule can assume two major C2 symmetric conformations. One of these has an all-trans X-Pro peptide backbone and two 1 comes from 4 intramolecular H-bonds and represents the predominant (greater than or equal to 95%) form in D2O and nonpolar (CD3CN) solvents. Stabilized by specific solvent-solute interactions, the other conformer becomes competitive (45%) in DMSO solution. It is shown to possess a four-cis X-Pro skeleton and no intramolecular H-bonds. The Mg++ complex of the cyclic peptide in CD3CN is again C2 symmetric and its formation proceeds via a slow trans leads to cis isomerization of two X-Pro peptide bonds.

Interaction of vanadate oligomers and permolybdate with the 90-kDa heat-shock protein, Hsp90.

The 90-kDa heat-shock protein (Hsp90) is a molecular chaperone that aids the folding of nuclear hormone receptors and protein kinases. Hsp90 x protein complexes can be stabilized by molybdate and by other transition metal oxyanions such as vanadate. Our earlier findings [Csermely, P., Kajtár, J., Hollósi, M., Jalsovszky, G., Holly, S., Kahn, C. R., Gergely, P. Jr, Söti, C., Mihály, K. & Somogyi, J. (1993) J. Biol. Chem. 268, 1901-1907] showed that vanadate and molybdate can induce a large conformational change of Hsp90. Here we provide direct evidence for the binding of vanadate and molybdate to Hsp90 by demonstrating that surface-plasmon-resonance measurements indicate binding of various vanadate oligomers to Hsp90. 51V-NMR measurements show an extensive interaction of decavanadate with the chaperone, and permolybdate treatment of Hsp90 induces a marked mobility shift of the protein and its tryptic fragments. Our results indicate the flexibility of molybdate/vanadate-binding sites of Hsp90, which are able to accommodate various species of these transition metal anions.

Zinc forms complexes with higher kinetical stability than calcium, 5-F-BAPTA as a good example.

Increasing interest is focused on the role of zinc in biological systems. A rapidly growing family of DNA-binding proteins contains "zinc-fingers", where zinc is bound to cysteine or histidine residues. On the other hand zinc is able to displace calcium from its binding sites and in this way it may modify calcium-mediated cellular processes. In the present report dissociation rates of Zn2(+)- and Ca2(+)-complexes with 5-F-BAPTA, a widely used NMR-active calcium indicator, have been measured by two-dimensional 19F NMR exchange spectroscopic methods. The results show that the lifetime of the Zn2(+)-complex is more than five times longer than that of the Ca2(+)-complex. The longer lifetime, when combined with a higher thermodynamical stability of the Zn2+-complex, may explain why, in some cellular processes, Zn2+ can compete with Ca2+ in spite of a presumably high [Ca2+]/[Zn2+] free ion concentration ratio.