• Title/Summary/Keyword: Guanine

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Base Specificity for DNA Interstrand Cross-Linking Induced by Anticancer Agent Bizelesin

  • Lee, Chong-Soon;Myung, Pyung-Keun;Gibson, Neil W.
    • Archives of Pharmacal Research
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    • v.19 no.3
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    • pp.191-196
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    • 1996
  • Bizelesin is a promising novel anticancer agent which is known to alkylate N3 of adenine to induce DNA interstrand cross-links (ISC) with in $5^I-TAATTA\; and\; 5^I-TAAAAAA$. We have investigated the base specificity for DNA ISC induced by bizelesin using oligomers containing the cross-linkable sequence $5^I-TAATTA\; and\; 5^I-TAAAAAA$. in which "N" was either A, C, G, or T. An analysis of denaturing polyacrylamide gel showed that bizelesin is able to induce DNA ISC in the duplex oligomer containing sequences $5^I-TAATTA\; and\; 5^I-TAAAAAA$. The formation of interstrand crosslinking did not occur in the sequences $5^I-TAATTA\; and\; 5^I-TAAAAAA$. DNA strand cleavage assay to determine the cross-linking site within $5^I-TAATTA$sequence showed that bizelesin alkylates guanine. These results demonstrate that bizelesin is able to induce DNA ISC at guanine but not at cytosine or thymine. In addition, guanine adducts have been found to be susceptible to DNA strand cleavage by exposure to hot piperidine. The extent of DNA strand cleavage, however, was not 100% efficient in either neutral pH buffer or hot piperidine.

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The Suppressive Effect of Medicinal Herbs on the $H_2O_2$-Induced Hypoxanthine-Guanine Phosphoribosyl Transferase (HPRT) Mutation (수종의 생약이 과산화수소에 의한 Hypoxanthine-guanine Phosphoribosyl Transferase (HPRT) 유전자 돌연변이 억제에 미치는 효과)

  • You, Ho-Jin;Woo, Eun-Rhan
    • Korean Journal of Pharmacognosy
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    • v.35 no.1 s.136
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    • pp.28-34
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    • 2004
  • DNA damage induced by reactive oxygen species (ROS) seems to play an important role in the induction of mutation and cancer. Hydrogen peroxide $(H_2O_2)$ has been shown to induce a variety of genetic alterations, probably by the generation of hydroxyl radicals via Fenton reaction. In this study, we examined the ability of medicinal herbs in the suppression of $H_2O_2$-induced mutagenesis. Human fibroblast GM00637 cells were treated with $H_2O_2$ in the presence or absence of medicinal herbs, and $H_2O_2$-induced mutant frequency was measured at the hypoxanthine guanine phosphoribosyl transferase (HPRT) locus. Treatment of cells with various doses of $H_2O_2$ caused a significant increase of the HPRT mutant frequency. However, pretreatment of cells with several medicinal herbs reduced $H_2O_2$-induced mutant frequency. The strong antimutagenic effects were observed from the methylene chloride and ethyl acetate fractions of Selaginella tamariscina, Panax ginseng, and Angelica acutiloba; ethyl acetate fractions of Rehmania glutinosa, Leonurus sibiricus, Curcuma zedoaria and Commiphora molmol; butanol fractions of Scutellaria barbata, Tribulus terrestris, Curcuma zedoaria, Cyperus rotundus and Carthamus tinctorius, which were more than 60% inhibition of $H_2O_2$-induced mutant frequency at the HPRT locus.

Mechanism of guanine-specific DNA damage by UVA and its role in photocarcinogenesis and photoaging

  • Kawanishi, Shosuke;Oikawa, Shinji;Hiraku, Yusuke
    • Journal of Photoscience
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    • v.9 no.2
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    • pp.150-153
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    • 2002
  • Solar UV light is a well-known carcinogen. UVA radiation is probably carcinogenic to humans. In addition, recent investigations point to the importance of UVA irradiation in the photoaging. We investigated the mechanism of sequence- specific DNA damage using $\^$32/P-Iabeled DNA fragments in relation to carcinogenesis and aging. Furthermore, we investigated whether UVA accelerates the telomere shortening in human WI-38 fibroblasts. The exposure of double- stranded DNA fragments to 365 nm light in the presence of endogenous sensitizers produced sequence-specific cleavage at the 5' site of 5'-GG-3' and 5'-GGG-3' sequences. In addition, HPLC analysis revealed that sensitizers plus 365 nm light increased the 8-oxodG content of double-stranded DNA. We discuss the mechanisms of guanine-specific DNA damagecaused by excited photosensitizers in relation to carcinogenesis and aging.

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Ric-8B Modulates the Function of Alpha Subunit of Go

  • Kim, Seung-Hyun;Ghil, Sung-Ho
    • Biomedical Science Letters
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    • v.13 no.2
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    • pp.127-133
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    • 2007
  • Heterotrimeric GTP binding proteins (G proteins) mediate signal generated by neurotransmitter and hormones. Among all G proteins, Go is the most abundant in brain but its role in brain is not clearly understood. To determine the function of the alpha subunit of Go (Go$\alpha$), we search for the interacting partner of Go$\alpha$ in brain using yeast two-hybrid system. A resistant to inhibitor of cholinesterase (Ric-8B) was identified as a Go$\alpha$ interacting protein. We confirmed interaction between Go$\alpha$ and Ric-8b employing in vitro affinity binding assay and showed that the Ric-8b increased the function of Go$\alpha$. Our findings indicate that Ric-8b is possible guanine nucleotide exchange factor for Go$\alpha$.

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ANALYSIS OF GUANINE PLUS CYTOSINE CONTENTS OF DNA OF Butyrivibrio fibrisolvens BY HIGH PERFORMANCE LIQUID CHROMATOGRAPHY (HPLC)

  • Nakatani, M.;Kohda, C.;Inamoto, T.;Nakai, Y.;Ogimoto, K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.7 no.4
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    • pp.509-512
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    • 1994
  • High performance liquid chromatography (HPLC) analysis was applied for determination of guanine plus cytosine (G + C) contents of DNA of Butyrivibrio fibrisolvens. By values of G + C contents, a reference strain and 20 wild strains of B. fibrisolvens were classified into at least two distinct subgroups, i.e. G + C contents of 18 strains were 38-40 mol% and those of 3 strains including the reference strain were 43-45 mol%. Clear relationships were not observed between G + C contents and biological properties of 21 strains of B. Fibrisolvens.

The Status of Guanine Nucleotides in Taxol-Stabilized Microtubules Probed by 31P CPMAS NMR Spectroscopy

  • Ferdous, Taslima;Lee, Sang-Hak;Yeo, Kwon-Joo;Paik, Youn-Kee
    • Journal of the Korean Magnetic Resonance Society
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    • v.15 no.2
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    • pp.104-114
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    • 2011
  • Rapid exchange and hydrolysis of the tubulin-bound guanine nucleotides have been known to govern the dynamics of microtubules. However, the instability and low concentration have made it difficult for the microtubule-bound GTP to be observed directly. In this study, we circumvent these problems by lyophilization and using cross-polarization techniques. $^{31}P$ NMR signals were detected from the tubulin-bound GTP in microtubules for the first time. Analysis of the $^{31}P$ CPMAS NMR spectrum indicates that GTP hydrolysis was delayed by the presence of taxol.

Racemic Synthesis of Novel 6'-Methylene-5'-norcarbocyclic Purine Phosphonic Acid Analogues via Mitsunobu Reaction

  • Kim, Eun-Ae;Liu, Lian Jin;Hong, Joon-Hee
    • Bulletin of the Korean Chemical Society
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    • v.32 no.8
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    • pp.2689-2694
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    • 2011
  • Novel 5'-norcarbocyclic adenine and guanine phosphonic acid analogues with 6'-electronegative moiety such as unsaturated C-C bond were designed and synthesized from commercially available 2-methylene-propane-1,3-diol (4). Regioselective Mitsunobu reaction successfully proceeded from an allylic functional group (${\pm}$)-12b at low reaction temperature in polar cosolvent (DMF/1,4-dioxane) to give purine phosphonate analogues (${\pm}$)-13 and (${\pm}$)-20. The purine nucleoside phosphonate and phosphonic acid analogues were subjected to antiviral screening against HIV-1. Guanine analogue (${\pm}$)-23 shows significant anti-HIV activity in PBM cell lines ($EC_{50}=8.1\;{\mu}M$).

Effects of Pertussis Toxin on Macrophage Activation

  • Lim, Suck-Ihn;An, Nyeon-Hyoung
    • Archives of Pharmacal Research
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    • v.15 no.2
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    • pp.146-151
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    • 1992
  • The aim of this study was to evaluate capability of pertussis toxin (PT) to active mouse macrophages. The investigations were undertaken to determine whether the role played by this toxin required the A-protomer of the toxin to ADP-ribosylate a guanine nucleotide binding protein (a class I activity) or was dependent on the binding of B-oligomer of the toxin to the surface of target cells (a Class II activity). The results of these experiments have established that the mechanism of macrophage activation with PT seems to be dependent upon a Class II activity of the toxin.

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