• Archives of Pharmacal Research
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• 제28권7호
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• pp.745-749
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• 2005

A simple synthetic route for the synthesis of novel methyl branched cyclopropyl phosphonic acid nucleosides is described. The characteristic cyclopropyl moiety 8 was constructed by employing Simmons-Smith reaction as a key step. The condensation of mesylate 11 with natural nucleosidic bases (A,C,T,U) under standard nucleophilic substitution conditions ($K_2CO_3$, 18-Crown-6, DMF) and after subsequent hydrolysis resulted in the formation of target nucleosides, 16, 17, 18, and 19. In addition, the antiviral evaluations of the synthesized nucleotides against various viruses were also performed.

• International Journal of Industrial Entomology and Biomaterials
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• 제7권2호
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• pp.139-144
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• 2003

Over 350 million people worldwide are chronic carriers of hepatitis B virus (HBV). Chronic viral infections of the liver can progress to cirrhosis, which may ultimately lead to hepatic failure or the development of hepatocellular carcinoma. There are two antiviral drugs on the market approved for clinical management of chronic HBV infections; interferon-alpha and the nucleoside analog lamivudine. However, they showed adverse side-effects. In the rational drug design for such therapies we would like to utilize antiviral drugs that inhibit the HBV replication in the liver. Investigation of natural extracts of silkworm exhibiting antiviral potential was held in the functional HBV polymerase activity and the release of virion particle in the HepG2.2.15 cell lines. HBV-producing transgenic mouse fed with silkworm DNJ molecule was shown as an inhibitor of serum HBV particles. We could represent this DNJ molecule as an antiviral potential complementing conventional therapies after preclinical tests against WHBV-infected animal model, woodchuck.

• Bulletin of the Korean Chemical Society
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• 제27권5호
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• pp.613-630
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• 2006

Nucleic acids are virtually omnipresent; they exist in every living being. These macromolecules constitute the most important genetic storage material: the genes. Genes are conserved throughout the evolution of all living beings; they are transmitted from the parents to their offspring. Many interdisciplinary research groups are interested in modifying nucleic acids for use in a wider variety of applications. These modified oligonucleotides are used in many diverse fields, including diagnostics, detection, and therapeutics. In this account, we summarize our research efforts related to modified nucleic acid systems. First, we discuss our syntheses of modified oligonucleotides containing fluorescent tags for use as molecular probes (molecular beacons) to detect single-nucleotide polymorphisim (SNP) in nucleic acids and to distinguish between the B and Z forms of DNA. We also describe our research efforts into oligonucleotides functionalized with steroid derivatives to enhance their cell permeability, and the synthesis of several calix[4]arene-oligonucleotide conjugates possessing the ability to form defined triplexes. In addition, we have performed systematic studies to have an understanding about the functional groups necessary for a given nucleoside to behave as an organo or hydrogelator. The aggregation properties of a number of nucleoside-based phospholipids have been examined in different solvents; some of these derivatives are potential candidates for use as nucleoside-based liposomes. Finally, we also describe our research efforts toward the preparation of isoxazole- and isoxazoline-containing nucleoside derivatives and the determination of their antiviral activities.

• Bulletin of the Korean Chemical Society
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• 제32권8호
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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 ($EC_{50}=8.1\;{\mu}M$).

• Bulletin of the Korean Chemical Society
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• 제31권11호
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• pp.3348-3352
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• 2010

Novel 4'-ethyl-5'-norcarbocyclic adenosine phosphonic acid analogues were synthesized from propionaldehyde 5 through a de novo acyclic synthetic route using reiterative Grignard additions and ring-closing metathesis (RCM) as key reactions. The synthesized nucleoside phosphonic acids analogues 17, 18, 19, and 21 were subjected to antiviral screening against human immunodeficiency virus.

• Archives of Pharmacal Research
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• 제25권6호
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• pp.790-794
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• 2002

A series of novel exomethylene cyclopropyl nucleosides have been synthesized starting from Feist's acid. Classical nucleophilic substitution conditions ($K_2CO_3$, 18-crown-6) of the tosylate 2 as well as Mitsunobu reaction (DEAD, $PPh_3$) of alcohol 1 with pyrimidine bases afforded a series of novel cyclopropyl nucleosides. Compound 4b displayed moderate anti-HBV activity without any cytotoxicity up to $100{\;}{\mu}M$.

• 한국잠사학회:학술대회논문집
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• 한국잠사학회 2003년도 International Symposium of Silkworm/Insect Biotechnology and Annual Meeting of Korea Society of Sericultural Science
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• pp.28-33
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• 2003

Over 100 million people worldwide are chronic carriers of hepatitis C virus (HCV)(1). Chronic viral infections of the liver can prouess to cirrhosis, which may ultimately lead to hepatic failure or the development of hepatocellular carcinoma. There are a limited number of antiviral drugs on the market approved fur clinical management of chronic HCV infections; interferon-alpha (IFN$\alpha$) and the nucleoside analog ribavirin. However, whether used as monotherapy or in combination, adverse side-effects are associated with each drug and better therapeutic regimens are needed. (omitted)

• Bulletin of the Korean Chemical Society
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• 제34권12호
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• pp.3621-3628
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• 2013

Novel 5'-deoxythreosyl purine phosphonic acid analogues containing a 2'-electropositive moiety such as fluorine atom, were designed and synthesized from commercially available 1,3-dihydroxy acetone. Condensation successfully proceeded from a glycosyl donor 6 under Vorbr$\ddot{u}$ggen conditions and cross-metathesis gave the desired phosphonate analogues 7a, 7b, 17a and 17b. The synthesized nucleoside phosphonic acid analogues 13, 16, 23, 26, 28 were subjected to antiviral screening against HIV-1. The bis(SATE) adenine analogue 28 exhibited significant in vitro activities against HIV-1.

• Bulletin of the Korean Chemical Society
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• 제31권8호
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• pp.2180-2184
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• 2010

We synthesized and tested the anti-HIV activity of the SATE prodrug of a 2'-methyl 5'-norcarbocyclic adenine analogue. The introduction of a methyl group in the 2'-position was performed by the addition of a carbonyl using isopropenyl magnesium bromide. The adenine base was efficiently coupled using the Mitsunobu reaction. The chemical stability study of the bis(SATE) derivative 18 was measured at neutral (pH 7.2) and slightly acid (milli-Q water, pH 5.5) pH, and compounds 16 and 18 were evaluated as potential anti-HIV-1 agents.

• 약학회지
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• 제52권6호
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• pp.466-470
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• 2008

Human cytomegalovirus expresses an unusual protein kinase UL97, a member of ${H_V}{U_L}$ family of protein kinase. UL97 can phosphorylate nucleoside analogs such as ganciclovir as well as protein/peptide. It has previously been reported that UL97 is able to phosphorylate a KESYSVYVYKV peptide and that P+5 position (K) is important. We examined the extent of contribution of other positions (P-4 through P+6) of the peptide to be substrate of UL97 using alanine substituted peptides (Ala scanning) and deleted peptides. The result suggested that the E (P-2) is negative effect and P+5 (K) is still important. The peptide YSVYVYK is the shortest substrate enough to show high activity, which could be a starting point to develop peptidomimetic drug. This study would give important information to deeply understand the substrate specificity of UL97 and develop an antiviral drug using the small peptide identified here.