• Journal of Environmental Science International
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• v.7 no.1
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• pp.52-56
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• 1998

The effects of organophosphorus and carbamate pesticides were examined inhibition of the acetylcholinesterase activity in the chicken brain with enzyme-inhibition methods. The acetylcholinesterase activity in chicken brain determined by the Ellman method was 167 mmol/min/g protein. The optimum pH of acetycholinesterase was 8.2. $pl_{50}$ of acetycholinesterase by some organophosphorus were 3.80M of phosphorodlthioate, 4.04M of phosphorothioate, 6.33M of phosphate, and 6.60M of phosphrothiolate. pluto of acetycholinesterase by some carbamates were 5.1 OM of XMC, 5. 90M of carbofuran, 6.16M of isoprocarb, 6.30M of carbaryl, 6.47M of BPMC, and 6.77M of propoxur. pluto of carbamates selected was similar to that of phosphorothioate and phosphate organophosphates.

• BMB Reports
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• v.36 no.6
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• pp.529-532
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• 2003

The potential physiological role and technological application of the premature termination of DNA polymerization through the off-switch of exo+ polymerases were studied using 3' phosphorothioate-modified or unmodified primers with single base mismatch distal to the 3' terminus. With exonuclease-digestible unmodified primers, a gradient premature termination of DNA polymerization was observed when amplified with exo+ polymerases. With 3' allele specific phosphorothioate-modified primers, an efficient off-switch effect occurred in the discrimination of a single nucleotide polymorphism when directly using genomic DNA. Clearly, the off-switch of exo+ polymerases is useful in biomedical research.

• Journal of Pharmaceutical Investigation
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• v.25 no.4
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• pp.347-351
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• 1995

Antisense phosphorothioate oligodeoxynucleotide(PS-ODN) against $TGF-{\beta}$ was developed as scar formation inhibitor. The scar was caused collagen deposition due to overexpression of $TGF-{\beta}$ in wounded skin. The percutaneous absorption of partially modified PS-ODN(25 mer) was investigated for the purpose of its effective delivery. Though PS-ODN has high molecular weight (MW=8,000) and polyanionic charge, it was permeated through skin. The skin permeation of PS-ODN was markedly increased by the removal of stratum corneum and dermis. Moreover, the skin permeation of PS-ODN was decreased in the following order; hairless mouse skin>rat skin>human cadaver skin. Thus, PS-ODN represents a logical candidate for further evalution due to the potential for delivery into the wounded skin.

• Bulletin of the Korean Chemical Society
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• v.17 no.1
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• pp.24-28
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• 1996

A procedure is described for the synthesis of the title compound via phosphotriester intermediates. The preparation of $R_p$ and $S_p$ diastereomeric dinucleotide of d[Cp(S)T] was performed by the condensation of the protected deoxycytidine, the protected thymidine, 2,5-dichlorophenylphosphorodichloridothioate and 1-hydroxybenzotriazole in THF. Their designation of configuration at phosphorus as $R_p$ and $S_p$ follows from anaylsis of ${31}^P$ NMR spectroscopy and reverse-phase HPLC and the stereospecificity in the hydrolysis catalyzed by Nuclease S1 and snake venom phosphodiesterase. Diastereomerically pure $R_p$ and $S_p$ d[Cp(S)T] were utilized to synthesize oligonucleotides containing the XhoI recognition sequence with a phosphorothioate group at the cleavage site.

• Molecules and Cells
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• v.38 no.2
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• pp.122-129
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• 2015

DBM-2198, a six-membered azasugar nucleotide (6-AZN)-containing phosphorothioate (P = S) oligonucleotide (AZPSON), was described in our previous publication [Lee et al. (2005)] with regard to its antiviral activity against a broad spectrum of HIV-1 variants. This report describes the mechanisms underlying the anti-HIV-1 properties of DBM-2198. The LTR-mediated reporter assay indicated that the anti-HIV-1 activity of DBM-2198 is attributed to an extracellular mode of action rather than intracellular sequence-specific antisense activity. Nevertheless, the antiviral properties of DBM-2198 and other AZPSONs were highly restricted to HIV-1. Unlike other P = S oligonucleotides, DBM-2198 caused no host cell activation upon administration to cultures. HIV-1 that was pre-incubated with DBM-2198 did not show any infectivity towards host cells whereas host cells pre-incubated with DBM-2198 remained susceptible to HIV-1 infection, suggesting that DBM-2198 acts on the virus particle rather than cell surface molecules in the inhibition of HIV-1 infection. Competition assays for binding to HIV-1 envelope protein with anti-gp120 and anti-V3 antibodies revealed that DBM-2198 acts on the viral attachment site of HIV-1 gp120, but not on the V3 region. This report provides a better understanding of the antiviral mechanism of DBM-2198 and may contribute to the development of a potential therapeutic drug against a broad spectrum of HIV-1 variants.

• The Korean Journal of Pesticide Science
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• v.5 no.1
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• pp.12-18
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• 2001

The effects of organophosphorus were examined with inhibition of the cholinesterase activity on tile chicken plasma in vivo and in vitro. The cholinesterase activity in chicken plasma determined by tile Ellman mettled was $23{\mu}mol$/min/g protein. After oral administration with 0.2 and 0.5 times of organophosphorus terbufos $LD_{50}$(1.81 mg/kg), cholinesterase activity were inhibited to 36% and 96% of control after 15min in vivo, respectively. After oral administration with 0.2 and 0.5 times of terbufos $LD_{50}$(1.81 mg/kg), then the recovery of cholinesterase activity followed to 99% and 56% of control after 11hr, respectively. Ki of phosphorodithioate and phosphorothioate with P=S was $74{\sim}322\;mole^{-1}min^{-1}$ in vitro. Ki of phosphate and phosphorothiolate with P=O was $13898{\sim}79610\;mole^{-1}min^{-1}$. Toxicology of organophosphorus with P=S was higher than that of organophosphorus with P=S by oxidation. $pI_{50}$ of phosphorodithioate and phosphorothioate with P=S was $21{\sim}102$ mg/L. $pI_{50}$ of phosphate and phosphorothiolate with P=O was $0.519{\sim}0.071$ mg/L. Enzyme-Inhibition method with cholinesterase was the rapid bioassay method to detect the organohpophorus pesticides in vitro.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.155-160
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• 2002

A series of modified oligonucleotides containing a phosphorothioate (P=S) backbone and a six-membered azasugar (6-AZS) as a sugar substitute in a nucleotide were synthesized and tested for their ability to inhibit the human immunodeficiency virus type I(HIV-l) in vitro without the aid of any transfecting agents. While P=S oligonucleotides with natural nucleotides had little anti-HIV-l activity, the six-membered azasugar nucleotide (6-AZN)-containing P=S oligonucleotides (AZPSONs) potently inhibited the HIV-l/SHIV replication and syncytium formation (ECso = 0.02-0.2 /lM) without cytotoxicity up to 100 /lM. DBM-2198, the most effective in anti-HIV-l activity among the AZPSONs, consists of random sequence and five 6¬AZNs evenly distributed in 18 nucleotides. DBM-2198 showed strong antiviral activity against, not only laboratory strains, but also primary isolates and even drug-resistant strains of HIV-I. DBM-2198 was much more effective than ddI or ddC in its anti-HIV-l activity in vitro. Particularly noteworthy is that the anti-HIV-l activity of DBM-2198 was better than that of AZT with respect to its long-lasting efficacy after a single treatment. Nevertheless, the antiviral activity of the AZPSONs was very specific to HIV-I. Poliovirus, or even simian immunodeficiency virus (SIV), was not inhibited by the AZPSONs. Taken together, our results strongly suggest that AZPSON can be used as a safe and effective AIDS-therapeutic drug against a broad spectrum of HIV -1 strains.

• Archives of Pharmacal Research
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• v.19 no.2
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• pp.116-121
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• 1996

Antisense oligonucleotides seem to provide a promising new tool for the therapy. Choi et al. (1995) reported antisense phosphorothioate oligonucleotides (PS-ODN, 25 mer) complementary to TGF-.betha. mRNA designed for scar formation inhibitor to eliminate scars, which was caused by undesired collagen deposition due to overexpression of TGF-.betha., in wounded skin. PS-ODN were evaluated in vitro for skin penetration using normal and tape-stripped damaged rat skin. The in vitro skin transports were carried out with partially modified PS-ODN (6S) and fully modified PS-ODN (25S). The cumulative amount of PS-ODN (6S) penetrated through normal rat skin was $0.234{\pm}0.041{\mu}g/cm^2$ and that of tape-stripped damaged rat skin was $1.077{\pm}0.301{\mu}g/cm^2$ over 8 hrs. PS-ODN (25S) can not be found in receptor medium through normal skin due to high molecular weight (Mol.Wt.=8,000) and polyanionic charge. However, the cumulative amount of PS-ODN (25S) penetrated across damaged rat skin in PBS was $0.340{\pm}0.296{\mu}g/cm^2$ over 8 hrs. The absense of dermis raised the cumulative amount of PS-ODN (6S) penetrated through rat skin. And the fluxes of PS-ODN (6S) and PSODN (25S) at 8hrs across damaged rat skin were $134.63{\pm}37.67{\mu}g/cm^2$ h, and $42.50{\pm}36.95ng/cm^2$ h, respectively. While PS-ODN (25S) was stable in 10% heat inactivated fetal bovine serum (FBS) during 24 hrs, PS-ODN (6S) was less stable than PS-ODN (25S), but was markedly stable than unmodified phosphodiester. It is suggested that the cumulative amount of PS-ODN (6S) penetrated through damaged rat skin is larger than that of PS-ODN (25S) since the former is easier to degrade by nuclease than the latter and then is apt to penetrate into skin. Thus, PS-ODN represents a logical candidate for further evaluation due to the potential for delivery into the wounded skin.

• Applied Biological Chemistry
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• v.33 no.2
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• pp.138-142
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• 1990

The effects of heavy metals Cd, Cu, Cr, Ni, and Zn on the degradation of the insecticide fenitrothion (O, O-dimethyl O-4-nitro-m-tolyl phosphorothioate), the fungicide IBP (5-benzyl O, O-diisopropyl phosphorothioate), and the herbicide butachlor (N-butoxymetyl-2-chloro-2', 6'-diethylacetanilide) in flooded soils were examined in the laboratory. The degradation of the 3 pesticides in soil was greatly inhibited by the amendment of the 5 heavy metals. The inhibition rate was high in the order of butachlor>IBP>fenitrothion. Populations of fenitrothion-and butachlor-degrading microbes, which were counted by the MPN method, were lower in heavy metals added soil than in the control soil. The effect of heavy metals on the degradation of the 3 pesticides in soil varied with the kind and concentration of heavy metals and the kind of pesticides.

• Toxicological Research
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• v.4 no.2
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• pp.107-115
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• 1988

The effects of altering the hepatic mixed-function oxidase(MFO) activities on the acute toxicity of parathion were examined in female rats. Phenobarbital sodium pretreatment (50mg/kg/day, i.p.) for 4 consecutive days has resulted in significant decreases in the toxicity of parathion (2 or 4 mg/kg, i.p.) as determined by lethality and cholinesterase activities wheras the toxicity arising from a single dose of CCl4(2 mmol/kg, i.p.) 24 hr prior to parathion challenge was potentiated.