• 한국임상약학회지
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• 제26권3호
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• pp.220-229
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• 2016

Background: The treatment goal for patients with chronic hepatitis B infection is to prevent progression of the disease to cirrhosis and hepatocellular carcinoma. Current therapies include standard and pegylated interferon-alfa and nucleoside/nucleotide analogues: lamivudine, adefovir, entecavir, telbivudine, clevudine, and tenofovir. This study aims to analyze changes in the prescribing patterns of chronic hepatitis B (CHB) medications in South Korea between 2013 and 2014. Methods: A cross-sectional study was conducted using National Patients Sample data compiled by the Health Insurance Review and Assessment Service from 2013 and 2014. Patients with CHB were identified with Korean Standard Classification of Diseases code-6 (B18.0 and B18.1) and those who were maintaining active prescriptions with CHB medications covering the index date (December $1^{st}$, each year) were included. The utilization of antiviral therapy was investigated during 2013 and 2014. Results: A total of 4,204 and 4,552 patients in 2013 and 2014 respectively, were included in the analysis. The proportion of male patients was two of third and the patients 41-60 years old accounted for 60% of all analyzed patients. The most utilized drug was entecavir (55.1% in 2013 and 44.8% in 2014) and the second most utilized drug was tenofovir in both years (18.8% in 2013 and 29.0% in 2014). The percentage of combination therapy was 13.6% and 13.1% in 2013 and 2014, respectively. The proportion of tenofovir prescriptions was increased in 2014 compared with 2013. Conclusion: With the development of new drugs and the changes in clinical practice guidelines, the prescription pattern of the antiviral agents for patients with CHB has changed. The rate of utilization of tenofovir has increased.

• Bulletin of the Korean Chemical Society
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• 제35권9호
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• pp.2743-2748
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• 2014

Novel 4'-trifluoromethyl-5'-norcarbocyclic purine phosphonic acid analogs were efficiently synthesized from commercially available 1,3-dihydroxy cyclopentane (5). Trifluoromethylation was successfully performed by using the Ruppert-Prakash reaction. The purine nucleosidic bases were efficiently coupled by using the Mitsunobu reaction. The synthesized adenosine phosphonic acids analogs 13 and 16 were screened for antiviral activity against human immunodeficiency virus-1 (HIV-1). Adenine derivative 13 exhibited significant anti-HIV-1 activity.

• Bulletin of the Korean Chemical Society
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• 제32권6호
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• pp.1931-1935
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• 2011

The synthesis of carbocyclic analogues of normal nucleosides has grown exclusively since they have shown potential antiviral and antitumor activities. Radiolabeled cis-1-[4-(hydroxy-methyl)-cyclopent-2-enyl]-5-$[^{124}I]$-iodocytosine (carbocyclic d4IC) and cis-1-[4-(hydroxy-methyl)-cyclopent-2-enyl]-5-(2-$[^{124}I]$iodovinyl)cytosine(carbocyclic d4IVC) were synthesized. The synthetic route employed Pd(0)-catalyzed coupling reaction together with organotin and exchange reaction for radioiodination as key reactions. Carbocyclic $[^{124}I]$d4IC gave more than 75% radiochemical yield with greater than 95% radiochemical purity. Carbocyclic $[^{124}I]$d4IVC gave more than 80% radiochemical yield with greater than 95% radiochemical purity.

• Journal of Microbiology and Biotechnology
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• 제30권1호
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• pp.11-20
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• 2020

Quercetin and its derivatives are important metabolites that belong to the flavonol class of flavonoids. Quercetin and some of the conjugates have been approved by the FDA for human use. They are widely distributed among plants and have various biological activities, such as being anticancer, antiviral, and antioxidant. Hence, the biosynthesis of novel derivatives is an important field of research. Glycosylation and methylation are two important modification strategies that have long been used and have resulted in many novel metabolites that are not present in natural sources. A strategy for modifying quercetin in E. coli by means of glycosylation, for example, involves overexpressing respective glycosyltransferases (GTs) in the host and metabolic engineering for increasing nucleoside diphosphate sugar (NDP-sugar). Still others have used microorganisms other than E. coli, such as Streptomyces sp., for the biotransformation process. The overall study of the structural activity relationship has revealed that modification of some residues in quercetin decreased one activity but increased others. This review summarizes all of the information mentioned above.

• 약학회지
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• 제50권4호
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• pp.268-271
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• 2006

Protein kinase UL97 is an unusual protein kinase that can phosphorylate nucleoside analogs as well as protein/peptide. Previously we found a H2B-derived peptide, KESYSVYVYKV and reported that the P+5 position (K) is important. To further understand the substrate specificity at the P+5 position, we introduced spot assay system and showed that a peptide containing K residue among other amino acids at the P+5 position is the best substrate. Also other residues such as M, I, L, or G are good enough to be substrate of UL97. This result may aid the discovery of a new antiviral inhibitor.

• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.341.1-341.1
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• 2002

Apio nucleosides belong to unique classes of nucleosides in that 4'-hydroxymethyl group moves to 3'-position. Among thse compounds. we found that apio dideoxyadenosine (apio-ddA) exhibited potent antiviral activity and apio-d4A showed potent anti-HCMV activity. Based on thse findings. it was of great interest to design and synthesize Anio nucleoside anlogues with various substituents such as fluorn or azido group. In order to synthesize apio analogues. the glyxosyl dondr. D-. and L-apio sugar acetates were first synthesized. starting from D-gallas. condensed whth silylated N4-benzoylcytosine. and then convenged to the linal D-andL-nucleosides. Synthesist of the D-and-apio nucieosides will be prssented in detail aht th the meeting.

• Molecules and Cells
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• 제40권6호
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• pp.418-425
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• 2017

Interferon-${\gamma}$-inducible protein 10 (IP-10), also known as chemokine C-X-C motif ligand (CXCL) 10, is closely associated with antiviral immunity and the progression of chronic hepatitis B (CHB). However, the value of baseline serological and histological IP-10 expression levels in predicting the efficacy of the antiviral response to nucleoside/nucleotide analogues (NAs) is still unknown. In our research, intrahepatic and peripheral IP-10 expression levels were systemically examined before and after treatment with entecavir (ETV). Baseline serological and histological IP-10 expression levels were significantly increased in patients with CHB, particularly in patients with higher degrees of liver inflammation and liver fibrosis. Moreover, higher baseline intrahepatic IP-10 levels indicated better prognoses in patients with CHB after entecavir therapy. The baseline IP-10 level was also positively associated with several clinical parameters, including baseline levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hepatitis B virus (HBV) DNA, and hepatitis B surface antigen (HBsAg), and with the decrease in HBsAg levels after treatment. In addition, monocyte-derived IP-10 was expressed at higher levels in patients with CHB than in patients with liver cirrhosis (LC) and healthy controls (HC). According to the results of our in vitro experiments, IP-10 directly promoted hepatocyte apoptosis. Based on these findings, baseline serological and histological IP-10 levels might predict CHB severity and the decrease in HBsAg levels after entecavir therapy.

• BMB Reports
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• 제37권2호
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• pp.167-176
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• 2004

Although efficient antiviral lamivudine is used for HBV-infected patients, a prolonged treatment with nucleoside analogs often results in lamivudine-resistant variants. In this study, we evaluated the fidelity of the lamivudine-resistant variants. The FLAG-tagged wild-type (FPolE) and Met550 variants (FPolE/M550A, M550V, and M550I) of HBV DNA polymerases were expressed in insect cells then purified. Like many other reverse transcriptases, no $3'{\rightarrow}5'$ exonuclease activity was detected in the HBV DNA polymerase. Since there is no proofreading activity, then the use of the site-specific nucleotide misincorporation method is beneficial. From the $f_{ins}$ value analysis, it is evident that M550I and M550V exhibit higher fidelity values than the wild-type HBV DNA polymerase, while M550A exhibits similar fidelity values. It is therefore suggested that lamivudine resistance comes from the stringency to dNTP binding and the discrimination of dCTP and lamivudine in M550V and M550I.

• Bulletin of the Korean Chemical Society
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• 제35권9호
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• pp.2649-2654
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• 2014

Synthesis of north-5'-methylbicyclo[3.1.0]hexyl adenine and hypoxanthine nucleosides with an ethenyl group at C3' position was successfully achieved by a highly facile method. Methylbicyclo[3.1.0]hexanone (${\pm}$)-7 with three contiguous chiral centers and its epimer (${\pm}$)-6 was remarkably simply constructed only by four steps involving a carbenoid insertion reaction in the presence of rhodium (II) acetate dimer as a metal catalyst, giving a correct relative stereochemistry of the generated three chiral centers. Due to steric hindrance from the concave face of the bicyclo[3.1.0]hexanone system, a Grignard reaction of (${\pm}$)-7 with ethenylmagnesium bromide showed exclusive diastereoselectivity towards the b-face. The Grignard reaction chemoselectively proceeded without reacting with ester functionality. Coupling reaction of glycosyl donor (${\pm}$)-11 with 6-chloropurine nucleobase afforded only the desired $N^9$-alkylated nucleoside without the formation of $N^7$-regioisomer. By the conventional method, 6-chloro group was converted into 6-amino and 6-hydroxy groups to give the desired adenine and hypoxanthine bicyclo[3.1.0]hexyl carbanucleosides with 3'-ethenyl group, respectively.

• Bulletin of the Korean Chemical Society
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• 제31권11호
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• pp.3309-3312
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• 2010

D-[$^{18}F$]FMAU and L-[$^{18}F$]FMAU are F-18 labeled nucleoside analogue which have been efficiently synthesized in order to be a PET imaging probe. D-[$^{18}F$]FMAU and L-[$^{18}F$]FMAU were compared as PET imaging agents using HSV1-TK gene expressing tumor-bearing mice. Their cellular uptake profiles were also compared using MCA and MCA-TK cell lines. D-[$^{18}F$]FMAU demonstrated higher cellular uptake and higher accumulation in MCA-TK tumor regions than L-[$^{18}F$]FMAU. On the other hand, L-[$^{18}F$]FMAU showed higher MCA-TK/MCA ratio of %ID/g than that of D-[$^{18}F$]FMAU. L-[$^{18}F$]FMAU can be utilized as a good candidate for HSV1-TK PET imaging. It can be used for antiviral drug evaluation.