• 제목/요약/키워드: Minor groove

검색결과 33건 처리시간 0.022초

이미다졸의 양성자 친화도에 미치는 치환기 효과에 대한 이론적 연구 (Theoretical Study for the Substituent Effect on Proton Affinity of Imidazoles)

  • 이현미;이갑룡
    • 대한화학회지
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    • 제38권1호
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    • pp.21-25
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    • 1994
  • 이미다졸 고리를 포함하는 lexitropsin에서, DNA minor grooved의 염기쌍(G-C sequence)과 결합하는 부분인 치환이미다졸의 양성자 친화도를 확장분자궤도함수법으로 조사하였다. 그 결과 메틸이미다졸의 경우 염기중심 질소의 $\alpha$위치에 치환된 이미다졸이 N에 치환된 이미다졸보다 양성자 친화도가 약간 더 크게 나타났으며 다른 치환이미다졸의 경우에는 N에 치환된 이미다졸이 ${\alpha}$위치에 치환된 이미다졸보다 양성자 친화도가 더 크게 나타났다. 예상한 바와 같이 이미다졸의 N에 전자를 미는기가 치환될 때 모두 양성자 친화도가 증가함을 알 수 있었다.

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미소전극어에이형 DNA칩을 이용한 유전자의 전기화학적 검출 (Electrochemical Detection of Genes Using Microeledtrode Array DNA Chip)

  • 최용성;박대희
    • 대한전기학회:학술대회논문집
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    • 대한전기학회 2004년도 하계학술대회 논문집 C
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    • pp.2125-2127
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    • 2004
  • In this paper, a DNA chip with a microelectrode array was fabricated using microfabrication technology. Several probe DNAs consisting of mercaptohexyl moiety at their 5 end were immobilized on the gold electrodes by DNA arrayer. Then target DNAs were hybridized and reacted with Hoechst 33258, which is a DNA minor groove binder and electrochemically active dye. Linear sweep voltammetry or cyclic voltammetry showed a difference between target DNA and control DNA in the anodic peak current values. It was derived from Hoechst 33258 concentrated at the electrode surface through association with formed hybrid. It suggested that this DNA chip could recognize the sequence specific genes.

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미소전극어레이형 DNA칩을 이용한 유전자의 전기화학적 검출 (Eletrochemical Detection of Gene using Microelectrode-array DNA Chip)

  • 최용성;권영수;;박대희
    • 한국전기전자재료학회논문지
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    • 제17권7호
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    • pp.729-737
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    • 2004
  • In this paper, a DNA chip with a microelectrode array was fabricated using microfabrication technology. Several probe DNAs consisting of mercaptohexyl moiety at their 5 end were immobilized on the gold electrodes by DNA arrayer. Then target DNAs were hybridized and reacted with Hoechst 33258, which is a DNA minor groove binder and electrochemically active dye. Linear sweep voltammetry or cyclic voltammetry showed a difference between target DNA and control DNA in the anodic peak current values. It was derived from Hoechst 33258 concentrated at the electrode surface through association with formed hybrid. It suggested that this DNA chip could recognize the sequence specific genes.

Binding Mode of [Ruthenium(II)$(1,10-Phenanthroline)_2L]^{2+}\;to\;Poly(dG){\cdot}poly( dC){\cdot}poly(dC)^+$ Triplex DNA

  • 조창범;조태섭;김복조;한성욱;정맹준
    • Bulletin of the Korean Chemical Society
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    • 제21권10호
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    • pp.1052-1054
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    • 2000
  • Binding geometries of $[Ru(II)(110-phenanthroline)_2L]^2+$, complexes (where L = dipyrido [3,2-a:2',3'-c]phena-zine (DPPZ) or benzodipyrido[3,2-a:2',3'-c] phenazine (BDPPZ)) to poly(dG)${\cdot}$poly(dC)${\cdot}$poly(dC) + triplex DNA (CGC + triplex) has been investigated by linear dichroism and normal absorption spectroscopy. Analysis of the linear dichroism for the CGC+ triplex and $[Ru(II)(phen)_2BDPPZ]^2+$ complex indicates that the extended ligand of the metal complex lie perpendicular to the polynucleotide helix axis. Together with strong hypochromism and red shift in the interligand absorption region, we concluded that the extended BDPPZ or DPPZ ligand in-tercalated between the bases of polynucleotide. The spectral properties of the metal complexes bound to CGC+ triplex are similar to those bound to $poly(dA)[poly(dT)]^2$ triplex (Choi et al., Biochemistry 1997, 36, 214), sug-gesting that the metal complex is located in the minor groove of the CGC+ triplex.

전기화학적 방법에 의한 유전자의 검출 (Genomic Detection using Electrochemical Method)

  • 최용성;이경섭;박대희
    • 한국전기전자재료학회논문지
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    • 제18권6호
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    • pp.560-570
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    • 2005
  • In this paper, a microelectrode away DNA chip was fabricated on glass slide using photolithography technology. Several probe DNAs consisting of mercaptohexyl moiety at their 5' end were immobilized on the gold electrodes by DNA arrayer utilizing the affinity between gold and sulfu. Then target DNAs were hybridized and reacted with Hoechst 33258, which is a DNA minor groove binder and electrochemically active dye. Cyclic voltammetry in 5mA ferricyanide/ferrocyanide solution at 100 mV/s confirmed the immobilization of probe DNA on the gold electrodes. Linear sweep voltammetry or cyclic voltammetry showed a difference between target DNA and control DNA in the anodic peak current values. It was derived from Hoechst 33258 concentrated at the electrode surface through association with formed hybrid. It suggested that this DNA chip could recognize the sequence specific genes. It suggested that multichannel electrochemical DNA microarray is useful to develop a portable device for clinical gene diagnostic system.

Sonographic Assessment of the Extent of Extrathyroidal Extension in Thyroid Cancer

  • Sae Rom Chung;Jung Hwan Baek;Young Jun Choi;Tae-Yon Sung;Dong Eun Song;Tae Yong Kim;Jeong Hyun Lee
    • Korean Journal of Radiology
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    • 제21권10호
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    • pp.1187-1195
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    • 2020
  • Objective: This study aimed to determine the sonographic features suggestive of extrathyroidal extension (ETE) of thyroid cancers. Materials and Methods: We retrospectively reviewed the sonographic images of 1656 consecutive patients who had undergone thyroidectomy in 2017. The diagnostic performance of sonographic features suggestive of ETE was evaluated using operation and histopathologic reports. Sonographic features for gross ETE to the strap muscle and minor ETE were assessed for thyroid cancer abutting the anterolateral thyroid capsule. Sonographic features for tracheal invasion were assessed according to whether the angle between the tumor and the trachea was an acute, right, or obtuse angle. Sonographic features for recurrent laryngeal nerve (RLN) invasion were assessed based on the association between the tumor and tracheoesophageal groove (TEG) as preserved normal tissue, abutting or protruding into the TEG. Results: ETE was observed in 783 patients (47.3%), including 123 patients with gross ETE (7.4% [strap muscle, n = 97; RLN, n = 24; and trachea, n = 14]) and 660 patients with minor ETE (39.9%). Regarding the diagnosis of gross and minor ETE to the strap muscle, sonographic features of replacement of the strap muscle and capsular disruption showed the highest positive predictive value (75.9% and 58.5%, respectively). Thyroid cancer forming an obtuse angle with the trachea had the highest sensitivity for the diagnosis of tracheal invasion (85.7%), and thyroid cancer protrusion into the TEG showed the highest sensitivity for the diagnosis of RLN (83.3%). Conclusion: Sonography is considered beneficial in the diagnosis of ETE to the strap muscle, trachea, and RLN. Assessment of ETE is important for the accurate staging of thyroid cancer, which in turn determines the extent of surgery or whether active surveillance is appropriate or not.

DNA Bis-intercalating Agent, Echinomycin-induced Apoptosis via Bcl-2 Dependence Pathway in Human Colon Cancer Cells

  • Park, Ju-Youn;Ryang, Yong-Suk;Kim, Jong-Bae;Chang, Jae-Ho;Cho, Hyeon-Cheol;Kim, Soo-Ki
    • Molecular & Cellular Toxicology
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    • 제4권2호
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    • pp.144-149
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    • 2008
  • Despite versatile activity (cancericidal, antimicrobial, hypoxia inducible factor (HIF) inhibition, immune deactivation of DNA bis-intercalation agent, echinomycin, its specific mechanism has been elusive. Of these novel mechanisms, we reported that using human colon cancer cells (HT-29), apoptotic machinery induced by echinomycin might be dependent of caspase-3 pathway. Despite a partial enlightenment of prototypic signal path triggered by echinomycin, the role of Bcl-2 in this signaling pathway is unclear. To address this issue, we explored whether or not echinomycin would overcome the anti-apoptotic impact of Bcl-2 in HT-29 cells by the controlled Bcl-2 overexpression. Prior to this proof, we confirmed that echinomycin induces mitochondrial depolarization, then triggering the mitochondrial pathway of apoptosis with an involvement of upstream cas-pases-3. Transiently transfection with inactive Bax-DNA failed to prevent echinomycin-induced apoptosis in HT-29 cells. To dissect the role of Bcl-2 in echinomycin-induced apoptosis, HT-29 cells were transiently transfected with Bcl-2 DNA for overexpression and then treated with echinomycin for 24h. Combined analyses of DNA fragmentation and flow cytometric analysis clearly verified that echinomycin-induced apoptosis was drastically attenuated by Bcl-2 overexpression, whereas a control vector rarely affected echinomycin-induced apoptosis. Collectively, these data verify that Bcl-2 regulates echinomycin-induced apoptosis in HT-29 cells. To my knowledge, this is the first evidence that of diverse, structured minor groove binders (MGB), the prototypic echinomycin might control the apoptotic signaling via Bcl-2-mitochondrial pathway.

Purification and Characterization of Hrp1, a Homolog of Mouse CHD1 from the Fission Yeast Schizosaccharomyces pombe

  • Yong Hwan Jin;Eung Jae Yoo;Yeun Kyu Jang;Seung Hae Kim;Chee-Gun Lee;Rho Hyun Seong;Seung Hwan Hong;Sang Dai Park
    • Animal cells and systems
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    • 제2권4호
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    • pp.539-543
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    • 1998
  • Hrp1, of Schizosaccharomyces pombe, is a new member of the SW12/SNF2 protein family that contains a chromodomain and a DNA binding domain as well as ATPase/7 helicase domains. This configuration suggests that Hrp1 could be a homolog of mouse CHD1, which is thought to function in altering the chromatin structure to facilitate gene expression. To understand the enzymatic nature of Hrp1 we purified the 6-Histidine-tagged Hrp1 protein (6$\times$His-Hrp1) to homogeneity from a S. pombe Hrp1-overexpressing strain and hen examined its biochemical properties. We demonstrate that the purified 6$\times$His-Hrp1 protein exhibited a DNA-binding activity with a moderate preference to the (A+T)-rich tract in double-stranded NA via a minor groove interaction. However, we failed to detect any intrinsic DNA helicase activity from the purified Hrp1 like other SW12/SNF2 proteins. These observations suggest that the DNA binding activities of Hrp1 may be involved in the remodeling of the chromatin structure with DNA-dependent ATPase. We propose that Hrp1 may function in heterochromatins as other proteins with a chromo- or ATPase/helicase domain and play an important role in the determination of chromatin architecture.

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Effects of Hin Recombinase Dimer Interface Mutants on DNA Binding and Recombination

  • Lee, Hee-Jung;Lee, Sun-Young;Lee, Hee-Jin;Lim, Heon-Man
    • 한국미생물생명공학회:학술대회논문집
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    • 한국미생물생명공학회 2001년도 Proceedings of 2001 International Symposium
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    • pp.27-31
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    • 2001
  • Previous biochemical assays and a structural model indicated that the dimer interface of the Hin recombinase is composed of the two a-helices. To elucidate the structure and function of the helix, amino acids in the N-terminal end of the helix, where the two helices contact most, were randomized, and inversion-incompetent mutants were selected. To investigate why the mutants lost their inversion activities, the DNA binding, hix-pairing, invertasome formation, and DNA cleavage activities were assayed using in vivo and in vitro methodologies. Results indicated that the mutants could be divided into 4 classes based on their DNA binding activity. We proposed that the a-helices might place a DNA binding motif of Hin properly to the minor DNA groove of the recombination site. All the mutants except the non-binders were able to perform hix-pairing and invertasome formation, suggesting that the dimer interface is not involved in the process of hix-pairing or invertasome formation. The inversion-incompetent phenotype of the binders was caused by the inability of mutants to perform the DNA cleavage activity. The less binders exhibited wild-type level of hix-pairing activity because the hix-pairing activity overcomes the DNA binding defect of the less binders. This phenotype of the less binders suggests that the binding domains of Hin could mediate Hin-Hin interaction during hix-pairing..

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Evidence for a Common Molecular Basis for Sequence Recognition of N3-Guanine and N3-Adenine DNA Adducts Involving the Covalent Bonding Reaction of (+)-CC-1065

  • Park, Hyun-Ju
    • Archives of Pharmacal Research
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    • 제25권1호
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    • pp.11-24
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    • 2002
  • The antitumor antibiotic (+)-CC-1065 can alkylate N3 of guanine in certain sequences. A previous high-field $^1H$ NMR study on the$(+)-CC-1065d[GCGCAATTG*CGC]_2$ adduct ($^*$ indicates the drug alkylation site) showed that drag modification on N3 of guanine results in protonation of the cross-strand cytosine [Park, H-J.; Hurley, L. H. J. Am. Chem. Soc.1997, 119,629]. In this contribution we describe a further analysis of the NMR data sets together with restrained molecular dynamics. This study provides not only a solution structure of the (+)-CC-1065(N3- guanine) DNA duplex adduct but also new insight into the molecular basis for the sequence- specific interaction between (+)-CC-1065 and N3-guanine in the DNA duplex. On the basis of NOESY data, we propose that the narrow minor groove at the 7T8T step and conformational kinks at the junctions of 16C17A and 18A19T are both related to DNA bending in the drugDNA adduct. Analysis of the one-dimensional $^1H$ NMR (in $H_2O$) data and rMD trajectories strongly suggests that hydrogen bonding linkages between the 8-OH group of the (+)-CC-1065 A-sub-unit and the 9G10C phosphate via a water molecule are present. All the phenomena observed here in the (+)-CC-1065(N3-guanine) adduct at 5'$-AATTG^*$are reminiscent of those obtained from the studies on the (+)-CC-1065(N3-adenine) adduct at $5'-AGTTA^*$, suggesting that (+)-CC-1065 takes advantage of the conformational flexibility of the 5'-TPu step to entrap the bent structure required for the covalent bonding reaction. This study reveals a common molecular basis for (+)-CC-1065 alkylation at both $5'-TTG^*$ and $5'-TTA^*$, which involves a trapping out of sequence-dependent DNA conformational flexibility as well as sequence-dependent general acid and general base catalysis by duplex DNA.