Asterriquinones produced by Aspergillus candidus inhibit binding of the Grb-2 adapter to phosphorylated EGF receptor tyrosine kinase.
(57/6255)
Five new asterriquinone analogs (2-4, 6, 7), together with previously identified neoasterriquinone (1) and isoasterriquinone (5), were isolated from a fermentation broth of the fungus Aspergillus candidus and purified by HSCCC (high speed counter current chromatography) followed by HPLC. The structures were determined by 1D and 2D NMR and MS/MS techniques. All seven showed inhibitory activity against the binding of a recombinant protein containing the SH2 protein domain of Grb-2 to the tyrosine phosphorylated form of the EGF receptor tyrosine kinase. Some of these asterriquinones exhibited specific inhibition of Grb-2 binding compared to Grb-7 and PLC-gamma. (+info)
Glucolipsin A and B, two new glucokinase activators produced by Streptomyces purpurogeniscleroticus and Nocardia vaccinii.
(58/6255)
During the screening of the natural products for their ability to increase the activity of glucokinase by relieving inhibition by long chain fatty acyl CoA esters (FAC), two novel compounds, glucolipsin A (1) and B (2) were isolated from the butanol extracts of Streptomyces purpurogeniscleroticus WC71634 and Nocardia vaccinii WC65712, respectively. The structures of these two compounds were established by spectroscopic methods and chemical degradation. Glucolipsin A (1) and B (2) relieved the inhibition of glucokinase by FAC with RC50 values of 5.4 and 4.6 microM. (+info)
Novel naphthoquinones from a Streptomyces sp.
(59/6255)
Cdc25A assay-guided fractionation of a fermentation broth derived from a Streptomyces sp. resulted in the isolation of four novel naphthoquinones 1-4. Structures of these compounds were deduced by NMR and mass spectrometry. Two of them, 3 and 4, incorporate a modified cysteine residue which is observed for the first time in this class of natural products. Naphthoquinones 1-4 showed weak activity against cdc25A phosphatase. (+info)
Gilvusmycin, a new antitumor antibiotic related to CC-1065.
(60/6255)
A new antitumor antibiotic gilvusmycin was isolated from the culture broth of Streptomyces sp. QM16. The structure of gilvusmycin was related to CC-1065 and determined by NMR spectral analysis. Gilvusmycin exhibited antitumor activity against murine leukemia P388 in vivo. (+info)
A 2,2"-bipyridine ligand for incorporation into oligodeoxynucleotides: synthesis, stability and fluorescence properties of ruthenium-DNA complexes.
(61/6255)
A non-nucleoside linker based upon the ligand 2,2'-bipyridine and ethylene glycol is prepared and placed into the backbone of a number of oligonucleo-tides. The bipyridine ligand is reacted with cis -dichloro bis(2,2'-bipyridyl) Ru(II) to generate the relatively substitutionally inert complex based upon the well-characterized tris -2,2'-bipyridyl Ru(II). The ruthenium-containing DNA complexes exhibited UV and fluorescence characteristics that are consistent with those previously observed for simple tris -2,2'-bipyridyl Ru(II) complexes. Oligonucleotides containing the ruthenium complex will form both DNA duplexes and triplexes with stabilities that are slightly better than those formed from simple tethered oligonucleotide probes in which the two hybridizing sequences are tethered by simple tri(ethylene glycol) or hexa(ethylene glycol) linkers. (+info)
Analysis of the cooperative thermal unfolding of the td intron of bacteriophage T4.
(62/6255)
The thermal stability of folded transcripts of the td intron of bacteriophage T4 that carried up to three base substitutions was investigated by temperature gradient gel electrophoresis (TGGE) and UV melting. The unfolding of this autocatalytic group I intron is endothermic and entropically driven. Although the effects of mutations in base pairs follow in most cases the expected order G-C>A-U>G.U>A.C, the extent of global destabilization varies strongly according to the helix in which substitutions are located. Effects are more pronounced in the P7 helix which forms, together with the P3 helix, the central pseudoknot of group I introns. The stability of the tertiary fold was also monitored as a function of ionic concentration and of the nature of the ion. At low ionic strength, the stabilizing effect of divalent ions is independent of the nature of the ion. However, with increasing ionic concentration, stabilization is most pronounced for Mg2+and less for Mn2+with Ca2+having intermediate effects. Ammonium ions stabilize folding with a similar slope, but at concentrations about 400 times higher than divalent ions. The apparent enthalpic change associated with the tertiary structure thermal unfolding increases strongly with increasing concentrations of divalent ions. A similar increase is observed with the monovalent ammonium ions. However, in the presence of NH4+ions, the apparent enthalpy peaks at 2.0 M and decreases beyond. (+info)
(2E,6R)-8-hydroxy-2,6-dimethyl-2-octenoic acid, a novel anti-osteoporotic monoterpene, isolated from Cistanche salsa.
(63/6255)
(2E,6R)-8-Hydroxy-2,6-dimethyl-2-octenoic acid [(R)-HDOA], a novel monoterpene from Cistanche salsa, a Chinese herb, was found to be an anti-osteoporotic compound. The extract of Cistanche salsa significantly suppressed the bone weight loss in ovariectomized mice, a postmenopausal osteoporosis model. The active substance was then purified by using this osteoporotic model and the chemical structure was determined. The active compound from Cistanche salsa, (R)-HDOA, suppressed the decrease of bone weight and the mechanical strength in the ovariectomized mice. Furthermore, (R)- and (S)-HDOA were synthesized and the activity of each was evaluated. (R)-HDOA suppressed the bone weight loss, although (S)-HDOA did not showed any activity. (+info)
Isolation and structural determination of a novel bicyclic taxane diterpene from needles of the Chinese yew, Taxus mairei.
(64/6255)
A novel bicyclic taxane diterpene with a rare 12-membered ring was isolated from needles of the Chinese yew, Taxus mairei, and its structure was established as (3E, 8E)-2 alpha, 7 beta, 9, 10 beta, 13 alpha, 20-hexaacetoxy-5(2'-acetoxy-cinnamoyloxy)-3,8-secotaxa -3,8,11-triene (1) with the help of 1D and 2D NMR data. The relative stereochemistry was deduced from a NOESY experiment. (+info)