Disease relevance of NSC 526417

• In the present study, endonuclease-restricted PM2 phage or pBR322 plasmid DNA fragments were treated with the bifunctional intercalative antitumor antibiotics, luzopeptin A (BBM-928A) and echinomycin, and analyzed by agarose gel electrophoresis [1].
• Enzymatic analysis of triostin A-producing Streptomyces triostinicus and quinomycin A-producing Streptomyces echinatus revealed four nonribosomal peptide synthetase modules for the assembly of the quinoxalinoyl tetrapeptide backbone of the quinoxaline antibiotics [2].
• The technique of DNAase I footprinting has been used to investigate preferred binding sites for echinomycin on a 160-base-pair DNA fragment from E. coli containing the tyr T promoter sequence [3].
• Compound 1QN bound most tightly to Micrococcus lysodeikticus DNA and, like echinomycin, exhibited a broad preference for (G + C)-rich DNA species [4].
• Seventeen patients were treated with echinomycin for metastatic renal cell carcinoma [5].

High impact information on NSC 526417

• This method reveals that echinomycin has a binding site size of four base pairs [6].
• Unstable Hoogsteen base pairs adjacent to echinomycin binding sites within a DNA duplex [7].
• In an effort to find evidence for Hoogsteen base-pairing at quinoxaline-binding sites in solution, chemical "footprinting" (differential cleavage reactivity) of echinomycin bound to DNA restriction fragments was examined [8].
• Both 1 and 2 were found to exhibit exceptional cytotoxic activity (IC(50) = 200 and 400 pM, respectively, L1210 cell line) comparable to echinomycin and one analogue, which bears the luzopeptin chromophore, was also found to be a potent cytotoxic agent [9].
• We have studied the binding of echinomycin to DNA fragments containing GC-rich regions flanked by blocks of alternating AT by DNase I footprinting and diethylpyrocarbonate modification [10].

Chemical compound and disease context of NSC 526417

• For quinomycin C the highest binding constant was found with Micrococcus lysodeikticus DNA, and its pattern of specificity among natural DNA species was broadly similar to that of echinomycin, although the binding constants were 2--6 times as large [11].
• The short-term effects on restenosis and thrombosis of echinomycin-eluting stents topcoated with a hydrophobic heparin-containing polymer [12].
• Streptomyces echinatus A8331 cultured on a maltose minimal salts medium normally produces a single antibiotic, echinomycin (quinomycin A), containing two quinoxaline-2-carbonyl chromophores [13].
• Newly modified-echinomycin such as S-methylated sulfonium perchlorate of echinomycin (1), monosulfoxide (2), disulfoxid (3) and sulfone (4) have been prepared and evaluated for in vitro biological activities of cytotoxicity against P388, B16 and SNU-16 as well as in vivo antitumor activity against murine leukemia P388 and melanoma B16 [14].

Biological context of NSC 526417

• Echinomycin binding sites on DNA [6].
• Moreover, preventing the possibility of Hoogsteen base pairing does not preclude echinomycin binding [15].
• Limited evidence for slow reaction with echinomycin and mithramycin is presented, but the kinetics of footprinting with daunomycin and distamycin appear instantaneous [16].
• The hypothesis that echinomycin locates its preferred nucleotide sequences in DNA by a process of "shuffling" between potential binding sites has been tested [17].
• With both DNAase I and MPE.FeII, enhanced DNA cleavage is evident at AT-rich sequences in the presence of echinomycin [18].

Anatomical context of NSC 526417

• When nucleosome cores reconstituted from chicken erythrocyte histones and a 160 bp DNA molecule are exposed to echinomycin, a bis-intercalating antitumour antibiotic, the DNA appears to rotate with respect to the histone octamer by about half a turn [19].
• Echinomycin suppresses the pyrogenic effects of endotoxin and interleukin-1 beta in human endothelial cells and peripheral blood mononuclear cells [20].
• A phase II trial of echinomycin in metastatic cervix carcinoma [21].
• Molecular signaling cascade in DNA bisintercalator, echinomycin-induced apoptosis of HT-29 cells: evidence of the apoptotic process via activation of the cytochrome c-ERK-caspase-3 pathway [22].
• PD98059 treatment or overexpression of kinase-inactive ERK did not alter the echinomycin-induced cytochrome c release into the cytosol, but did diminish the activation of procaspase-3 [22].

Associations of NSC 526417 with other chemical compounds

• Moreover, a 12-base-pair segment of alternating A-T DNA, which is 6 base pairs away from the nearest strong echinomycin-binding site, is also hyperreactive to diethyl pyrocarbonate in the presence of echinomycin [8].
• Interaction of nucleosome core particles with distamycin and echinomycin: analysis of the effect of DNA sequences [23].
• In the case of echinomycin only one purine 2-amino group is required for remarkably strong binding to the asymmetric TpDAP.TpA dinucleotide step, but the CpDAP.TpI step (which also contains only a single purine-2 amino group) does not afford a binding site [24].
• Further experiments were performed with echinomycin at pH 5.5 and 4.6 to facilitate the protonation of cytosine required for formation of Hoogsteen GC base pairs [25].
• There are intermolecular hydrogen bonds between each of the Ala NH and the AN3 protons of the TpA binding site, analogous to those observed between Ala NH and GN3 in the crystal structures of the CpG-specific complexes of echinomycin and triostin A with DNA [26].

Gene context of NSC 526417

• These observations demonstrate that echinomycin protects endothelial cells and PBMC from the pyrogenic effect of LPS and IL-1 beta [20].
• Echinomycin also reduced LPS-induced secretion of IL-1 beta and IL-6 by human PBMC (IC50 = 10 +/- 2 and 3 +/- 0.5 nM respectively) [20].
• It seems that certain sequences, mainly runs of A or runs of T, switch from a nuclease-resistant to a nuclease-sensitive form when echinomycin binds nearby [3].
• Taken together, these results indicate that cytochrome c release, and the activation of ERK and caspase-3 in the final apoptosis pathway are all relevant factors in echinomycin-induced apoptosis [22].

Analytical, diagnostic and therapeutic context of NSC 526417

• Atomic force microscopy study of the structural effects induced by echinomycin binding to DNA [27].
• The DNase I footprinting titration studies greatly refined the existing knowledge of the DNA-binding characteristics of echinomycin, as they revealed five general types of concentration-dependent behavior at single-bond resolution [28].
• Hydrophobic heparinized polymer was then topcoated onto stent over echinomycin/PU layer by dipping to improve hemocompatibility [12].
• The objective of this trial was to determine the efficacy of echinomycin (1.2 mg/m2) administered on a weekly times four schedule in the treatment of patients with recurrent or progressive central nervous malignancies despite adequate radiotherapy [29].
• For instance, against Bacillus anthracis strains, kakadumycin A has minimum inhibitory concentrations of 0.2-0.3 microg x ml(-1) in contrast to echinomycin at 1.0-1.2 microg x ml(-1) [30].

References