• Bulletin of the Korean Chemical Society
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• 제35권12호
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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.

• 대한화학회지
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• 제55권6호
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• pp.988-993
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• 2011

Cyclodehydration of 6-amino-5-cyano pyrimidine derivative (2) afforded pyrimidoisoindole derivatives (3). Compound (3) reacted with carbethoxymethylene derivative to give pyridopyrimidine derivatives (5a,b). Compound (3) was also reacted with formamide to give the corresponding pyrimidopyrimdine derivatives (6) that condensed with benzaldehyde to give Schiff's base (7). Refluxing of compound (3) with triethyl orthoformate afforded compound (8) that cyclized with ammonium hydroxide giving the same compound (6). Compound (8) cyclized with hydrazine hydrate giving compound (9) which also cyclized with triethyl orthoformate affording compound (10). Diazotization of compound (3) led to the formation of triazinopyrimidine derivative (11). Cyclization of compound (11) upon treatment with hydrazine hydrate afforded compound (12). Compound (15) was prepared from reaction of compound (3) and ethylenediamine in presence of carbon disulfide. The behaviour of compound (15) toward benzoyl chloride, triethyl orthoformate, nitrous acid and/or carbon disulfide was also described. All proposed structures were supported by elemental analyses, spectroscopic data and some of the new products showed antimicrobial activity.

• 대한화학회지
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• 제36권5호
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• pp.679-684
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• 1992

$trans-[Pd(en)_2Cl_2](ClO_4)-2$ (en = ethylenediamine)와 purine 염기인 Guanine, Adenine 또는 pyrimidine 염기인 Uracil anion을 반응시켜 새로운 팔라듐(IV) 착물을 얻었다. 착물의 중심금속과 각 리간드의 조성비는 $C{\cdot}H{\cdot}N$ 원소 분석으로써 확인하였으며 리간드의 배위자리 등 착물의 구조는 적외선 흡수 스펙트럼 및 $^1H-NMR,\; ^{13}C-NMR$로써 조사하였다. Guanine 또는 Adenine 착물을 purine계 염기가 N7 자리에 배위되었고 출발물질로부터 하나의 en 리간드가 이탈하고 두 $ClO_4^-$가 배위된 $[Pd(en)L_2(ClO_4)_2](ClO_4)_2{\cdot}(en)$ (L = Guanine, Adenine) 구조이다. Uracil 착물은 en과 $ClO_4^-$의 이동없이 Uracil anion의 N1 자리가 배위된 $[Pd(en)_2(Urac)_2](ClO_4)_2$ (Urac = Uracil anion) 구조의 착물로 추정되었다.

• 대한화학회지
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• 제53권3호
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• pp.244-256
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• 2009

소랄렌과 피리디민 염기와의 $C_4$-고리화 부가반응을 통한 가닥내 교차 결합(interstrand crosslinking) 에 의해 만들어진 소랄렌 복합체를 ab initio 방법인 HF와 DFT 6-31G 방법을 이용하여 연구하였다. 소랄렌과 피리디민 염기에 의해 만들어진 광생성물인 8-MOP< >Thy, Ps< >Cyt, Ps< >Thy, Ps< >Ps, Thy< >(3, 4)Ps(12, 13)< >Thy의 최적화된(optimized) 구조를 알 수 있으며, 8-MOP< >Thy은 (trans-syn) 구조, Ps(3, 4)< >Cyt은 (trans-anti) 구조, Ps(12, 13)< >Cyt은 (trans-anti) 구조, Ps(3, 4)< >Thy은 (trans-syn) 구조, Ps(12, 13)< >Thy은 (trans-syn) 구조가 가장 유리하다. Ps(3, 4)< >Thy과 Ps(12, 13)< >Thy의 Gibbs 자유 에너지 변화(${\Delta}{G^{\circ}}$)를 비교하면 Ps(12, 13)< >Thy의 광생성물(단일부가 생성물)이 이루어진 뒤에 Ps(3, 4)< >Thy의 광고리화 부가반응 생성물(이중부가 생성물)을 형성한다는 사실을 알 수 있다. Bispsoralen(psoralen dimer)에서는 Ps(12, 13)< >Ps(12, 13)(trans-anti) 구조가 가장 유리하며, Thy< >(3, 4)Ps(12, 13)< >Thy에서는 (cis syn)(cis anti) 형태가 가장 유리하다.

• 한국미생물생명공학회:학술대회논문집
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• 한국미생물생명공학회 1986년도 추계학술대회
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• pp.512.1-512
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• 1986

The cdd gene of Bacillus subtilis, encoding the deoxycytidinecytidine deaminase of pyrimidine nucleotide biosynthesis has been cloned into the EcoRl site of pBR322. The recombinant plasmid, pSol, promoted the synthesis of 100-140 fold elevated levels of the enzyme. A comparison of the polypeptides encoded by cdd complementing and non-complementing plasmids in the mini cell showed the gene product to have a molecular mass of approximately 14 kDa. The nucleotide sequence of the gene and 460 base pairs upstream from the coding region was determined. An open-reading frame, encoding a protein with a calculated molecular mass of 14337 Da, was deduced to be the coding region for cdd. However, the enzyme has an apparent molecular mass of 54 kDa as determined by gel filteration, whereas sucrose density gradient centrifugation shows 58 kDa. It means that the enzyme could be forming a tetramer in a physiological state. About 28 amino acids of the N-tetramer in a physiological state. About 28 amino acids of the N-terminal presumably form a signal for membrane translocation and six cystein residues are contained in the structure. S1 nuclease mapping indicated that transcription of cdd is initiated 17 base pairs upstream from the translational start. The structural characterization of the odd gene was performed.

• Journal of Microbiology and Biotechnology
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• 제17권7호
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• pp.1204-1207
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• 2007

Structural analyses have shown that nucleotides at the positions 770 and 771 of Escherichia coli 16S rRNA are implicated in forming one of highly conserved intersubunit bridges of the ribosome, B2c. To examine a functional role of these residues, base substitutions were introduced at these positions and mutant ribosomes were analyzed for their protein synthesis ability using a specialized ribosome system. The results showed requirement of a pyrimidine at the position 770 for ribosome function regardless of the nucleotide identity at the position 771. Sucrose gradient profiles of ribosomes revealed that the loss of protein-synthesis ability of mutant ribosome bearing a base substitution from C to G at the position 770 stems from its inability to form 70S ribosomes. These findings indicate involvement of nucleotide at the position 770, not 771, in ribosomal subunit association and provide a useful rRNA mutation that can be used as a target to investigate the physical interaction between 16S and 23S rRNA.

• BMB Reports
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• 제33권3호
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• pp.268-275
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• 2000

In contrast to the pyrimidine (6-4)pyrimidone photoproduct [(6-4) adduct], its Dewar valence isomer (Dewar product) is low mutagenic and produces a broad range of mutations with a 42 % replicating error frequency. In order to determine the origin of the mutagenic property of the Dewar product, we used experimental NMR restraints and molecular dynamics to determine the solution structure of a Dewar·lesion DNA decamer duplex, which contains a mismatched base pair between the 3'-T residue and an opposed G residue. The 3'-T of the Dewar lesion forms stable hydrogen bonds with the opposite G residue. The helical bending and unwinding angles of the DW/GA duplex, however, are much higher than those of the DW/AA duplex. The stable hydrogen bonding of the G 15 residue does not increase the thermal stability of the overall helix. It also does not restore the distorted backbone conformation of the DNA helix that is caused by the forming of a Dewar lesion. These structural features implicate that no thermal stability, or conformational benefits of G over A opposite the 3'-T of the Dewar lesion, facilitate the preferential incorporation of an A. This is in accordance with the A rule during translesion replication and leads to the low frequent $3'-T{\rightarrow}C$ mutation at this site.

• 한국동물학회지
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• 제26권3호
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• pp.171-179
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• 1983

MMS와 자외선에 의한 DNA의 절제회복과 단사절단에 미치는 poly(ADP-ribose) polymerase의 저해제인 3-aminobenzamide의 영향을 CHO 세포를 재로로 조사하여 다음과 같은 결과를 얻었다. 1. MMS에 의한 비주기성 DNA 합성률과 DNA 단사 절단률은 이 저해제에 의해 모두 증가하였다. 이는 poly (ADP-ribose) polymeraserk MMS에 의해 유발된 염기 절제회복의 incision step를 억제하는 결과라 생각된다. 2. 자외선에 의한 비주기성 DNA 합성률과 DNA단사 절단률은 이 저해제에 의해 모두 감소하였다. 이는 poly(ADP-ribose) polymerase가 자외선에 의해 유발된 nucleotide 절제회복의 incision step을 돕는 작용을 하는 결과로 생각된다. 3. MMS와 자외선을 복합처리한 실험군에서는, DNA 단사 절단률은 이 저해제에 의해 영향을 받지 않았으며, 비주기성 DNA 합성률은 자외선 단독 처리군의 수준으로 증가되었다. 이는, 이 저해제가 MMS와 자외선으로 유발된 절제회복의 incision step에는 독립적으로 작용하며, 그 이후의 단계에서, MMS에 의해 부분적으로 불활성화 되었던 pyrimidine dimers의 절제를 완전하게 해주는 것으로 해석된다.

• Journal of Photoscience
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• 제9권2호
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• pp.186-189
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• 2002

Many of the adverse effects of solar UV exposure appear to be directly attributable to damage to epidermal DNA. In particular, cyclobutane pyrimidine dimers (CPD) may initiate mutagenic changes as well as induce signal transduction responses that lead to a loss of skin immune surveillance and micro-destruction of skin structure. Our approach is to reverse the DNA damage using prokaryotic DNA repair enzymes delivered into skin using specially engineered liposomes. T4 endonuclease V encapsulated in liposomes (T4N5 liposome lotion) enhanced DNA repair by shifting repair of CPD from the nucleotide excision to the base excision repair pathway. Following topical application to humans, increased repair limited UV-induction of cytokines, many of which are immunosuppressive. In a recent clinical study, topical treatment of UV-irradiated human skin with T4N5 liposome lotion reduced the suppression of the nickel sulfate contact hypersensitivity response. Similarly, the photoreactivating enzyme enhances repair by directly reversing CPDs after absorbing activating light. Here also treatment of UV-irradiated human skin with photoreactivating enzyme in liposomes and photoreactivating light restored the response to the contact allergen nickel sulfate. These findings confirm in humans the observation in mice that UV induced suppression of contact hypersensitivity is caused in part by CPDs. We have tested the ability of T4N5 liposome lotion to prevent UV-induced skin cancer in patients with xeroderma pigmentosum (XP), who have an elevated incidence of skin cancer resulting from a genetic defect in DNA repair. Daily use of the lotion for one year in a group of 20 XP patients reduced the average number of actinic keratoses by 68% and basal cell cancers by 30% compared to 9 patients in the placebo control group. Delivery of DNA repair enzymes to skin is a promising new approach to photoprotection.

• Bulletin of the Korean Chemical Society
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• 제25권2호
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• pp.221-225
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• 2004

A series of 2',3'-dideoxy-3'-fluoro-D-apiosyl nucleosides 15, 16, 17 and 18 were synthesized enantiomerically with L-Gulonic- ${\gamma}$-lactone as the starting material. The reduction of butenolide 1 with DIBAL-H followed by the Luche procedure afforded the allylic alcohol 2. Ozonolysis and the reduction of compound 4 induced the cyclized lactol, which was acetylated to give the acetate 7. Condensation of the acetate 7 with silylated pyrimidine ($N^4$-benzoyl cytosine) and a purine base (6-chloropurine) under Vorbruggen conditions and deblocking afforded a series of fluorinated apiosyl nucleosides.