• Bulletin of the Korean Chemical Society
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• v.35 no.12
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• pp.3502-3508
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• 2014

The first synthetic route to 5'-norcarbocyclic C-nucleoside [7-oxa-7,9-dideazadenosine (furo[3,2-d]pyrimidine) and 9-deazaadenosine (pyrrolo[3,2-d]pyrimidine)] phosphonic acids from commercially available 1,3-dihydroxy cyclopentane was described. The key C-C bond formation from sugar to base precursor was performed using Knoevenagel-type condensation from a ketone derivative. Synthesized C-nucleoside phosphonic acids were tested for anti-HIV activity as well as anti-leukemic activity. Compound 26 showed significant anti-leukemic activity.

• Microbiology and Biotechnology Letters
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• v.28 no.5
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• pp.251-257
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• 2000

Serratia marcescens purine nucleoside phosphorylase (PNP) was purfied to homogeneity by streptomycin sulfate treatment, Sephacry HR S-200 gel filtration chromatography and AMP-agarose affinity chromatography. The specific activity of the enzyme was increased 49-fold during purification with an overall yield of 7.0%. The molecular weight was 168kD as estimated by Sephadex G-150 gel filtration chromatography. The S. marcescens enzyme was composed of six identical subunits with subunit molecular weight of 28kD, as estimated by SDS-PAGE. The Km values of S. marcescens enzyme for inosine and deoxyinsoine were 0.38 and 1.20 mM, respectively. The ph optimum was near 8.0, and the enzyme was relatively heat-stable protein. The enzyme was inactivated com-pletely by 0.5 mM of $Cu^{ 2+}$.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.10a
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• pp.67-69
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• 1995

reverse transcription은 AIDS를 일으킨다고 알려진 바이러스인 HIV-1의 번식에는 필수적이나 인체 세포에는 필수적이 아니기에 이 단계를 표적으로 하는 AIDS 치료제가 우선적으로 개발되었다. 그 단계에 필요한 효소가 바이러스에 의해 만들어진 RT이며 이 효소의 작용을 저해하는 nucleoside 유도체들인 AZT, DDC, DDI 들이 현재 AIDS 환자의 치료에 사용되고 있다. 이들 nucleoside 유도체들은 세포안으로 들어가 triphosphate 형태로 변화된 후 dNTP와 상경적으로 경쟁하며 합성 중인 바이러스의 DNA에 들어가 DNA의 합성을 정지시켜 바이러스의 증식을 억제한다. 그러나, 이들 nucleoside 유도체들은 치료용량에서 심한 독성을 나타낼 뿐만 아니라 장기 투여시 내성을 나타내는 바이러스가 생겨나 AIDS의 치료를 불가능하게 하고 있다.

• BMB Reports
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• v.35 no.4
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• pp.403-408
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• 2002

A hypothetical 21.0 kDa protein (ORF O197) from Escherichia coli K-12 was cloned, purified, and characterized. The protein sequence of ORF O197(termed EcO197) shares a 33.5% identity with that of a novel NTPase from Methanococcus jannaschii. The EcO197 protein was purified using Ni-NTA affinity chromatography, protease digestion, and gel filtration column. It hydrolyzed nucleoside triphosphates with an O6 atom-containing purine base to nucleoside monophosphate and pyrophosphate. The EcO197 protein had a strong preference for deoxyinosine triphosphate (dITP) and xanthosine triphosphate (XTP), while it had little activity in the standard nucleoside triphosphates (dATP, dCTP, dGTP, and dTTP). These aberrant nucleotides can be produced by oxidative deamination from purine nucleotides in cells; they are potentially mutagenic. The mutation protection mechanisms are caused by the incorporation into DNA of unwelcome nucleotides that are formed spontaneously. The EcO197 protein may function to eliminate specifically damaged purine nucleotide that contains the 6-keto group. This protein appears to be the first eubacterial dITP-and XTP-hydrolyzing enzyme that has been identified.

• Biomolecules & Therapeutics
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• v.3 no.2
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• pp.116-121
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• 1995

Some multidrug resistance inhibitors have been known to be influenced by the serum concentration. In this study, effect of serum concentration on inhibition of nucleoside transport by BIBW22, a new multidrug resistance inhibitor derived from dipyridamole (DPM), was studied. When 5% or 100% (v/v) of fetal bovine serum (FBS) was contained in the culture, DPM dose for which nucleoside transport was inhibited by 50% (lD$_{50}$) was 0.42 $\mu$M or 1.17 $\mu$M, respectively. BIBW22 also showed the same trend as DPM did in response to increase of FBS concentration. However, ID$_{50}$ value for DPM in the absence or presence of human plasma was 0.007 $\mu$M or 1.02 $\mu$M respectively showing 145 times increase of ID$_{50}$ value. ID$_{50}$ value for BIBW22 in the presence of human plasma was 0.028 $\mu$M showing only 5 times increase in ID$_{50}$ value. This result suggests that potency of BIBW22 was much less affected by the plasma concentration and BIBW22 could be a good candidate for a clinical use in multidrug resistance treatment.treatment.

• Archives of Pharmacal Research
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• v.20 no.3
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• pp.259-263
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• 1997

In the preparation of acyclic thymidine nucleoside analogues, $K_2CO_3$(or NaH) treated thymine in DMSO was alkylated with .omega.-chloroalkyl nitrite (Cl-(CH_2)n-CN; n=1, 2, 3, 4) to provide an isomeric mixture of 1-(${\omega}$-cyanoalkyl)thymine (2a-d) and 1,3-bis(${\omega}$-cyanoalkyl)thymine in approximately 5:1 ratios. Reduction of the cyano function 2a-d with $NaBH_{4}/CoCl_{2}$ center dot$ 6H_{2}O$gave the corresponding 1-(${\omega}$aminoalkyl)thymine (3a-d). The newly formed primary amino function in 3a-d was directly reacted with 2-chloroethylisocyanate to afford the 1-[.omega.($N^{I}$-2-chloroethylureido) alkyl]thymine (4a-d) in good yields. Nitrosation of 1-[5-($ N^{I}-2$-chloroethylureido)pentyl] thymine (4d) with glacial acetic acid and dry $NaNO_{2}$-powder in anhydrous $CH_{2}Cl_{2}$gave two types of regioisomeric nitrosoureas, 1-[5-($N^{I}$--chloroethyl-$N^{I}$--nitrosoureido)pentylithymine (5d) and 1-[5-($N^{I}-2$-chloroethyl-N-nitrosoureido)pentyllthymine in approximately 5 :1 ratios. The in vitro cytotoxicity of the synthesized compounds (2a-d, 3a-d, 4a-d and 5a-d) against three cell lines (K-562, P-388 and FM-3A) are measured as $IC^{50}$ values. Compounds 3b and 4c showed moderate activities against all three cell lines, and all other compounds were found to be not active.

• Natural Product Sciences
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• v.13 no.2
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• pp.140-143
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• 2007

Investigation of the chloroform soluble fraction of the red alga Liagora farinosa, collected from Hurghada at the Red Sea resulted in the isolation of three compounds; a nucleoside (thymidine) and two glycosides (methyl-${\beta}$-D-xylopyranoside and glycerol-2-${\alpha}$-D-glucopyranoside). The structures of the isolated compounds were established on the basis of different spectroscopic techniques as well as comparison with the previously published data. This is the first report for the isolation of the three compounds fron red algae; moreover, the compounds were examined for their antioxidant activity and showed variable activity.

• YAKHAK HOEJI
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• v.38 no.6
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• pp.703-711
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• 1994

We synthesized D-1,3-dioxolanyl acetate from D-mannose using Frazer-Reide reaction and D-1,3-oxathiolanyl acetate from either D-mannose or D-galactose in good yields. These acetates were conjugated with various disilylated pyrimidine base using trimethylsilyl trifluoromethane sulfonate as a Lewis acid catalyst to obtain 32 different D-nucleosides.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.229-229
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• 1994

선택성이 높고 뛰어난 약효를 지닌 항 바이러스제의 개발은 신약개발의 중요한 영역중에 하나이다. 현재 AIDS 치료제로 사용되고 AZT를 비롯하여 항virus 효과를 나타내는 약물의 대부분은 구조적으로 nucleoside계에 속하는 화합물로서 수 많은 약리학적 연구 및 합성 화학적 연구가 이루어져 왔다. 특히 합성 화학적 측면에서 이들 화합물의 합성은 크게 두가지로 나누어지는데 그것은 sugar 부위의 변형을 통한 방법과 염기 부위의 변형을 통한 방법에 의해 새로운 항 바이러스제를 개발하는 것이다. 최근의 연구 동향에 있어서 주목할 만한 변화의 하나는 sugar 부위의 구조적 변형을 시도하는데 있어서 종래의 5원환 형태에서 환이 개열된 형태의 acyclic nucleoside에 대한 연구가 이루어져 좋은 효과를 거두고 인다는 사실이다. Acyclovir, Ganciclovir등 의 개발이 그것이다. 본 연구에서는 종래의 acyclic nucleoside가 ribose sugar의 2'번 및 3'번 탄소를 제거한 acyclic ether 형태로 되어있는 것과는 다르게 ether 부위의 산소를 탄소 치환한 carbo-acyclic nucleoside를 합성하고자 하였다. Acyclic nucleoside를 합성하고자 하였다. Acyclic nucleoside의 side chain의 conformation이 항 바이러스 작용을 나타내는데 필수 불가결한 점을 감안할때, carbo-acyclic nucleoside계 화합물은 보다 다양하게 변형될 수 있는 장점을 가지고 있다. 이러한 관점에서 side chain의 2'번 및 3'번 탄소는 side chain의 conformation을 좌우하는 결정적 요인으로 작용할 것으로 판단된다. 따라서 본 연구에서는 이들 탄소를 중심으로한 분자수식을 시도하기로 하고 bioisosterism을 이용하여 3'위치의 수소를 fluoride로 치환한 화합물을 설계하여 합성을 시도하였다.silyl group-5'-무치환 화합물을 tosyl, azido화 한다음 desilylation하여 얻었다. 목적하는(1) 화합물의 diasteromer 인 2',3'-dihydroxy-5'-무치환 유도체(3)는 (4)화합물 합성시 얻은 hemiactal을 key intermediate로 하여 TsNHNH$_2$, NaB(CN)H$_3$ 및 NaOAc로 처리하므로서 얻을수 있었다. 이들 화합물들의 각종 DNA 및 RNA virus에 대한 항 바이러스작용을 검토한 결과 현저한 항 바이러스 작용을 나타내지 않았다.분화유도 활성을 나타내어 항종양제로의 개발에 많은 흥미가 기대된다.기대된다.oxylic acid (compound 10)를 합성하였다.10^{－7}$ M)에 의한 단백인산화에 대하여는 더 미약한 억제-효과를 나타내었다. 이상의 결과는 PDE-1과 항우울약들의 항혈소판작용은 PKC-기질인 41-43 kD와 20 kD의 인산화를 억제함에 기인되는 것으로 사료된다.다. 것으로 사료된다.다.바와 같이 MCl에서 작은 Dv 값을 갖는데, 이것은 CdCl$_{4}$$^{2-}$ 착이온을 형성하거나 ZnCl$_{4}$$^{2-}$ , ZnCl$_{3}$$^{-}$같은 이온과 MgCl$^{+}$, MgCl$_{2}$같은 이온종을 형성하기 때문인것 같다. 한편 어떠한 용리액에서던지 NH$_{4}$$^{+}$의 경우 Dv값이 제일 작았다. 바. 본 연구의 목적중의 하나인 인체유해 중금속이온인 Hg(II), Cd(II)등이 NaCl같은 염화물이 함유된 시료용액에 공해이온으로 존재할 경우 흡착에 의한 제거가 가능하다. 한편 이같은 중금속이온의 흡착실험은 특히 해수중의 금속이온의 회수연구에도

• Natural Product Sciences
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• v.13 no.3
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• pp.229-233
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• 2007

Chemical investigation of the crude extract of the Egyptian marine tunicate Eudistoma laysani led to the isolation of a new nucleoside; 3-deazainosine and four known ones; inosine, 2'-deoxyuridine, adenosine and 2'-deoxyadenosine. Structural elucidation of the isolated compounds was based on intensive studies of their spectral data including 1D ($^{1}H$ and $^{13}C$) and 2D ($^{1}H-^{1}H$ COSY, HMQC, HMBC) NMR together with mass spectra. The antioxidant effects of the isolated compounds were determined using DPPH, where they exhibited significant activities.