The bleomycins, a family of glycopeptides with antineoplastic activity, bind to DNA and cause strand-scission in reaction requiring Fe(I1) oxygen.Strandscission is accompanied by the simultaneous release free bases four low molecular weight compounds that react 2-thiobarbituric acid form chromophores absorbing maximally at 532 nm.The structure these products was elucidated as follows: formic hydrolysis released thymine, cytosine, adenine, guanine, respectively; treatment each compound...

The numbering system for nucleosides is also

The 8-oxoguanine-DNA glycosylase of Escherichia coli, also known as formamidopyrimidine-DNA (Fpg protein), has N-glycosylase and AP-lyase activities. This enzyme repairs oxidative DNA damage by efficiently removing formamidopyrimidine lesions 8-oxoguanine residues from DNA. Defined oligodeoxynucleotides containing various 8-oxopurines were used to examine the substrate specificity Fpg protein establish role functional groups in on recognition catalysis. Binding affinities established for...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNMR structural studies of the ionizing radiation adduct 7-hydro-8-oxodeoxyguanosine (8-oxo-7H-dG) opposite deoxyadenosine in a DNA duplex. 8-Oxo-7H-dG(syn).cntdot.dA(anti) alignment at lesion siteMichael Kouchakdjian, Veeraiah Bodepudi, Shinya Shibutani, Moises Eisenberg, Francis Johnson, Arthur P. Grollman, and Dinshaw J. PatelCite this: Biochemistry 1991, 30, 5, 1403–1412Publication Date (Print):February 1991Publication History Published online1...

Novel chemotherapeutics for treating multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) are required to combat the spread tuberculosis, a disease that kills more than 2 million people annually. Using structure-based drug design, we have developed series alkyl diphenyl ethers uncompetitive inhibitors InhA, enoyl reductase enzyme in MTB fatty acid biosynthesis pathway. The most potent compound has Ki' value 1 nM InhA and MIC99 values 2-3 microg mL(-1) (6-10 microM) both...

A single-stranded shuttle vector containing a single 3,N4-etheno-2'-deoxycytidine (epsilon dC) or 1,N2-(1,3-propano)-2'- deoxyguanosine (PdG) DNA adduct was used to investigate translesional synthesis in Escherichia coli and simian kidney (COS) cells. The presence of either exocyclic associated with reduced numbers transformants. In E. coli, this inhibitory effect could be overcome partially by irradiating cells UV light before transformation. Translesional past both lesions accompanied...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCompounds Related to Podophyllotoxin. XII. Podophyllotoxone, Picropodophyllone and Dehydropodophyllotoxin1Walter J. Gensler, Francis Johnson, A. David B. SloanCite this: Am. Chem. Soc. 1960, 82, 23, 6074–6081Publication Date (Print):December 1, 1960Publication History Published online1 May 2002Published inissue 1 December 1960https://pubs.acs.org/doi/10.1021/ja01508a026https://doi.org/10.1021/ja01508a026research-articleACS PublicationsRequest reuse...

A series of simple aza and diaza bicyclic quinones related to the AB ring system streptonigrin (1) have been synthesized tested in vitro for their ability degrade DNA under conditions similar those used with parent drug. The results obtained from a study 22 indicate that there is quantitative linear relationship between reduction potentials rate at which they identical vitro. Almost all synthetic substances were superior 1 DNA-degrading ability.

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSteric Interference in Allylic and Pseudo-Allylic Systems. I. Two Stereochemical TheoremsFrancis Johnson Sudarshan K. MalhotraCite this: J. Am. Chem. Soc. 1965, 87, 23, 5492–5493Publication Date (Print):December 1, 1965Publication History Published online1 May 2002Published inissue 1 December 1965https://pubs.acs.org/doi/10.1021/ja00951a046https://doi.org/10.1021/ja00951a046research-articleACS PublicationsRequest reuse permissionsArticle...

Exposure to aristolochic acid (AA), a component of Aristolochia plants used in herbal remedies, is associated with chronic kidney disease and urothelial carcinomas the upper urinary tract. Following metabolic activation, AA reacts dA dG residues DNA form aristolactam (AL)-DNA adducts. These mutagenic lesions generate unique TP53 mutation spectrum, dominated by A : T transversions mutations at located almost exclusively on non-transcribed strand. We determined level AL-dA adducts human...

Aristolochic acids (AAs) are a structurally related family of nephrotoxic and carcinogenic nitrophenanthrene compounds found in Aristolochia herbaceous plants, many which have been used worldwide for medicinal purposes. AAs implicated the etiology so-called Chinese herbs nephropathy Balkan endemic nephropathy. Both these disease syndromes associated with carcinomas upper urinary tract (UUC). 8-Methoxy-6-nitrophenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic acid (AA-I) is principal component...

The environmental and endogenous mutagen acrolein reacts with cellular DNA to produce several isomeric 1,N 2-propanodeoxyguanosine adducts. High resolution NMR spectroscopy was used establish the structural features of major acrolein-derived adduct, γ-OH-1,N 2-propano-2′-deoxyguanosine. In aqueous solution, this adduct shown assume a ring-closed form. contrast, when 2-propano-2′-deoxyguanosine pairs dC at center an 11-mer oligodeoxynucleotide duplex, exocyclic ring opens, enabling modified...

To understand how the active site of a DNA polymerase might modulate coding 8-oxo-7,8-dihydrodeoxyguanine (8-oxodG), we performed steady-state kinetic analyses using wild-type beta (pol beta) and two active-site mutants. We compared these polymerases by calculating ratio efficiencies for incorporation dATP dCTP opposite 8-oxodG 8-oxodGTP dA dC. For pol beta, there is 2:1 preference over 5'-phosphorylated 4-base gap substrate. Mutation either Asn279 or Arg283 to alanine has almost no effect...

To explore the molecular basis for picomolar affinity of triclosan FabI, enoyl reductase enzyme from type II fatty acid biosynthesis pathway in Escherichia coli, an SAR study has been conducted using a series analogues. Triclosan (1) is slow, tight-binding inhibitor interacting specifically with E.NAD(+) form K(1) value 7 pM. In contrast, 2-phenoxyphenol (2) binds equal to (K(1) = 0.5 microM) and E.NADH (K(2) 0.4 forms lacks slow-binding step observed triclosan. Thus, removal three chlorine...

Acrolein, which is widely spread in the environment and produced by lipid peroxidation cells, reacts with DNA to form two exocyclic 1,N2-propanodeoxyguanosine (PdG) adducts. To establish their relative contribution acrolein mutagenicity, genotoxic properties of α-OH-PdG γ-OH-PdG together model adduct, PdG, were studied human cells. adducts incorporated site-specifically into a SV40/BK virus origin-based shuttle vector replicated xeroderma pigmentosum complementation group A (XPA) Analysis...

Aristolochic acids I and II (AA-I, AA-II) are found in all Aristolochia species. Ingestion of these either the form herbal remedies or as contaminated wheat flour causes a dose-dependent chronic kidney failure characterized by renal tubulointerstitial fibrosis. In approximately 50% cases, condition is accompanied an upper urinary tract malignancy. The disease now termed aristolochic acid nephropathy (AAN). AA-I largely responsible for nephrotoxicity while both AA-II genotoxic. DNA adducts...

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSteric Interference in Allylic and Pseudo-Allylic Systems. II. Stereochemistry of Exocyclic Enolate Anion ProtonationSudarshan K. Malhotra Francis JohnsonCite this: J. Am. Chem. Soc. 1965, 87, 23, 5493–5495Publication Date (Print):December 1, 1965Publication History Published online1 May 2002Published inissue 1 December 1965https://doi.org/10.1021/ja00951a047Request reuse permissionsArticle Views345Altmetric-Citations60LEARN ABOUT THESE...

Matrix metalloproteinases (MMPs) are essential for the degradation and turnover of components extracellular matrix (ECM) and, when pathologically elevated, mediate connective tissue loss (including bone destruction) in various inflammatory other diseases. Tetracyclines (TCs) known inhibitors mammalian-derived MMPs, non-antibiotic formulations Doxycycline FDA-approved to treat periodontitis chronic skin disease, rosacea. Because C-11/ C-12 diketonic moiety tetracyclines is primarily...

Tetracycline-based matrix metalloproteinase- (MMP-) inhibitors are currently approved for two inflammatory diseases, periodontitis and rosacea. The current study addresses the therapeutic potential of a novel pleiotropic MMP-inhibitor not based on an antibiotic. To induce experimental periodontitis, endotoxin (LPS) was repeatedly injected into gingiva rats one side maxilla; contralateral (control) received saline injections. Two groups were treated by daily oral intubation with chemically...

Aristolochic acids are potent human carcinogens; the role of phase II metabolism in their bioactivation is unclear. Accordingly, we tested ability partially reduced metabolites, N-hydroxyaristolactams (AL-NOHs), and N-O-sulfonated N-O-acetylated derivatives to react with DNA form aristolactam–DNA adducts. AL-NOHs displayed little or no activity this regard while sulfo- acetyl compounds readily adducts, as detected by 32P-post-labeling analysis. Mouse hepatic renal cytosols stimulated binding...

Background and Objective Periodontal disease is the most common chronic inflammatory known to mankind (and major cause of tooth loss in adult population) has also been linked various systemic diseases, particularly diabetes mellitus. Based on literature linking periodontal with a “bidirectional manner”, objectives current study were determine: (i) effect model periodontitis, complicated by diabetes, mechanisms tissue breakdown including bone loss; (ii) response combination this local...

Epidemiological studies have linked aromatic amines (AAs) from tobacco smoke and some occupational exposures with bladder cancer risk. Several epidemiological also reported a plausible role for structurally related heterocyclic present in or formed cooked meats DNA adduct formation is an initial biochemical event carcinogenesis. We examined paired fresh-frozen (FR) formalin-fixed paraffin-embedded (FFPE) nontumor tissues 41 patients adducts of 4-aminobiphenyl (4-ABP), carcinogen smoke,...