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Synthesis and Antitumor Evaluation of cis-(1,2-Diaminoethane) dichloroplatinum (II) Complexes Linked to 5- and 6-Methyleneuracil and -uridine Analogues

  • Kim, Jack-C.;Lee, Min-Hwa;Choi, Soon-Kyu
    • Archives of Pharmacal Research
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    • v.21 no.4
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    • pp.465-469
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    • 1998
  • The search for platinum (II)-based compounds with improved therapeutic properties was prompted to design and synthesize a new family of water-soluble, third generation cis-diaminedichloroplatinum (II) complexes linked to uracil and uridine. Six heretofore unreported uracil and uridine-platinum (II) complexes are; [N-(uracil-5-yl-methyl)ethane-1,2-di-amine]dichloroplatinum (II) (3a), [N-(uracil-6-yl-methyl)ethane-1,2-diaminel dichloroplatinum (II) (3b), t[N-($2^1$, $3^1$,$5^1$-tri-O-acetyl)uridine-5-yl-methyl] ethane-1,2-diamineldichloroplatinum (II) (6a), {[N-($2^1$,$3^1$, $5^1$-tri-O-acetyl) uridine-6-yl-methyl]ethane-1,2-diamine)dichloroplatinum (II) (6b),[N-(uridine- 5-yl-methyl)ethane-1,2-diamine]dichloroplatinum (II) (7a), [N-(uridine-6-yl- methyl)ethane-1,2-diamine]dichloroplatinum (II) (7b). These analogues were prepared from the key starting materials, 5-chloromethyluracil (1a) and 6-chloromethyluracil (1b) which were reacted with ethylenediamine to afford the respective 5-[(2-aminoethyl)aminol methyluracil (2a) and 6-[(2-aminoethyl)amino]methyluracil (2b). The cis-platin complexes 3a and 3b were obtained through the reaction of the respective 2a and 2b with potassium tetrachloroplatinate (II). The heterocyclic nucleic acid bases 1a and 1b were efficiently introduced on the .betha.-D-ribose ring via a Vorbruggen-type nucleoside coupling procedure with hexamethyldisilazane, trimethylchlorosilane and stannic chloride under anhydrous acetonitrile to yield the stereospecific .betha.-anomeric 5-chloromethyl- $2^1$,$3^1$,$5^1$-tri-O-acetyluridine (4a) and 6-chloromethyl-$2^1$,$3^1$,$5^1$-tri-O-acetyluridine (4b), respectively. The nucleosides 4a and 4b were coupled with ethylenediamine to provide the respective 5-[(amino-ethyl)aminolmethyl-$2^1$,$3^1$,$5^1$-tri-O-acetyluridine (5a) and 6-[(aminoethyl)amino] methyl-$2^1$,$3^1$,$5^1$-tri-O-acetyluridine (5b). The diamino-uridines 5a and 5b were reacted with potassium tetrachloroplatinate (II) to give the novel nucleoside complexes, 6a and 6b, respectively which were deacetylated into the free nucleosides, 7a and 7b by the treatment with CH$_{3}$ONa. The cytotoxic activities were evaluated against three cell lines (FM-3A, P-388 and J-82) and none of the synthesized compounds showed any significant activity.

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IDEALS IN A TRIDIAGONAL ALGEBRA ALGL

  • LEE, SANG KI;KANG, JOO HO
    • Journal of applied mathematics & informatics
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    • v.34 no.3_4
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    • pp.257-267
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    • 2016
  • We find examples of Ideals in a tridiagonal algebra ALGL and study some properties of Ideals in ALGL. We prove the following theorems: Let k and j be fixed natural numbers. Let A be a subalgebra of ALGL and let A2,{k} ⊂ A ⊂ {T ∈ ALGL | T(2k-1,2k) = 0}. Then A is an ideal of ALGL if and only if A = A2,{k} where A2,{k} = {T ∈ ALGL | T(2k-1,2k) = 0, T(2k-1,2k-1) = T(2k,2k) = 0}. Let B be a subalgebra of ALGL such that B2,{j} ⊂ B ⊂ {T ∈ ALGL | T(2j+1,2j) = 0}. Then B is an ideal of ALGL if and only if B = B2,{j}, where B2,{j} = {T ∈ ALGL | T(2j+1,2j) = 0, T(2j,2j) = T(2j+1,2j+1) = 0}.

A Distribution Function Analysis of Photopic and Scotopic Curves (Photopic과 Scotopic 곡선의 분포함수 유도 및 분석)

  • Kim, Yong Geun
    • Journal of Korean Ophthalmic Optics Society
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    • v.5 no.2
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    • pp.157-161
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    • 2000
  • The Eye sensitivity in the difference conditions of a light source intensity consists of two functions by the receptor of cone and rod according to a wavelength. We derived a distribution function of $P({\lambda})=A{\cdot}e^{-({\lambda}-{\lambda}_0)^2/2W^2}$ using a respond probability of the receptor of cone-rod for a photon. It was well applied for a CIE eye's sensitivity curve of a wavelength, we obtained values in case of a relative sensitivity. A = 106.4, ${\lambda}_0=559.2$, W = 83.5 for a photopic and A = 99.3 ${\lambda}_0=502.6$, W = 79.5 for a scotopic, and in case of a sensitivity curve using 1m/W units. $A=7.2{\times}10^4$, ${\lambda}_0=559.2$, W = 83.5 for a photopic and $A=1.6{\times}10^5$, ${\lambda}_0=502.6$. W = 79.5 for a scotopic.

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ISOMORPHISM CLASSES OF HYPERELLIPTIC CURVES OF GENUS 2 OVER $F_{2_}{N}$ FOR EVEN n

  • Park, Chun-Soo;Rhee, Min-Surp
    • Journal of applied mathematics & informatics
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    • v.13 no.1_2
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    • pp.413-424
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    • 2003
  • L. H Encinas, A. J. Menezes and J. M. Masque in [3] proposed a classification of isomorphism classes of hyperelliptic curve of genus 2 over finite fields with characteristic different from 2 and 5. Y. Choie and D. Yun in [2] obtained the number of isomorphic classes of hyperelliptic curves of genus 2 over $F_{2-}$ using direct counting method. We have obtained isomorphism classes of hyperelliptic curves of genus 2 over $F_{2n}$ for odd n, represented by an equation of the form $y^2$ + $a_{5}$ y = $x^{5}$ + $a_{8}$ x + $a_{10}$ ( $a_{5}$ $\neq$0) [1]. In this paper we characterize hyperelliptic curves of genus 2 over $F_{2n}$ for even n, represented by an equation of the form $y^2$ + $a_{5}$ y = $x^{5}$ + $a_{5}$ x + $a_{10}$ ( $a_{5}$ $\neq$0).>0).

Two Possible Space Groups of Ttis(tekaethylammonium) [bis(trimetaphosphate $\kappa^3O, O^', O^{"}$)] Vanadate(3-),$[V(P_3O_9)_2](NC_8H_{20})3$ (Tris(tetraethylammnnium) [bis(trimetaphosphate $\kappa^3O, O^', O^{"}$)] Vamdate(3-),$[V(P_3O_9)_2](NC_8H_{20})_3$,의 두가지 가능한 공간군)

  • 서일환;이진호
    • Korean Journal of Crystallography
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    • v.5 no.1
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    • pp.1-6
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    • 1994
  • Two possible space groups of the comfound, VP6N3018C24H:60, are: P 1, a=14.022(1), b=12.644(2), c= 12.640(1)A, a=8038(1), B=102.12(1), r=102.16(1), V=2124.1A3, Z=2, μ=0.47cm-1, d=1.46g/cm3, R=0.083 for 3350 independent reflections with Fo>4o IFI, and C2/c, a=19.32(2), b=16.32(2), c=14.02(1)A, B=105.98(5), β=105.98(5), V=4248.2A3, Z=4 R=0.083 for 1590 independent reflections with Fo>4c IFoI . In the space group P T, there are two monlecules in a unit cell. Vanadium atoms in the two monlecules occupy the two different special positions such that the complete monlecules are accomplished by the two independent center of symmetry. Therefore two different half molecules of bis(trimetaphosphate)vanadate and three molecules of tetraethylammonium are the asymmetric unit in a unit cell. In the space group C2/c, however, the vanadium atom is located at a special position with centrosymmetry, and a two-fold symmetry axis passes through C2/c, N2 and C25 atoms. Therefore the asymmrtic unit in a unit cell consists of a half molecule of bis(trimetaphosphate)vanadate and one and a half molecules of tetraethylammonium. All the molecular conformations in both space groups are very similar: six oxygen atoms coordinated to a vanadium atom in the bi s(trimetaphosphate)vanadate molecule form an octahedron and the four carbon atoms bonded to a nitrogen atom in the tetraethylammonium molecule are disordered so that the eight carbon atoms around nitrogen atom exhibit an irregular dodecahedral form.

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Fusarium graminearum의 ZEB2 동형단백질에 의한 지랄레논 생합성 자가조절

  • Park, Ae Ran;Lee, Yin-Won
    • 한국균학회소식:학술대회논문집
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    • 2016.05a
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    • pp.27-27
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    • 2016
  • The ascomycete fungus Fusarium graminearum is the most common pathogen of Fusarium head blight (FHB), a devastating disease for major cereal crops worldwide. FHB causes significant crop losses by reducing grain yield and quality as well as contaminating cereals with trichothecenes and zearalenone (ZEA) that pose a serious threat to animal health and food safety. ZEA is a causative agent of hyperestrogenic syndrome in mammals and can result in reproductive disorders in farm animals. In F. graminearum, the ZEA biosynthetic cluster is composed of four genes, PKS4, PKS13, ZEB1, and ZEB2, which encode a reducing polyketide synthase, a nonreducing polyketide synthase, an isoamyl alcohol oxidase, and a transcription factor, respectively. Although it is known that ZEB2 primarily acts as a regulator of ZEA biosynthetic cluster genes, the mechanism underlying this regulation remains undetermined. In this study, two isoforms (ZEB2L and ZEB2S) from the ZEB2 gene in F. graminearum were characterized. It was revealed that ZEB2L contains a basic leucine zipper (bZIP) DNA-binding domain at the N-terminus, whereas ZEB2S is an N-terminally truncated form of ZEB2L that lacks the bZIP domain. Interestingly, ZEA triggered the induction of both ZEB2L and ZEB2S transcription. In ZEA producing condition, the expression of ZEB2S transcripts via alternative promoter usage was directly or indirectly initiated by ZEA. Physical interaction between ZEB2L and ZEB2L as well as between ZEB2L and ZEB2S was observed in the nucleus. The ZEB2S-ZEB2S interaction was detected in both the cytosol and the nucleus. ZEB2L-ZEB2L oligomers activated ZEA biosynthetic cluster genes, including ZEB2L. ZEB2S inhibited ZEB2L transcription by forming ZEB2L-ZEB2S heterodimers, which reduced the DNA-binding activity of ZEB2L. This study provides insight into the autoregulation of ZEB2 expression by alternative promoter usage and a feedback loop during ZEA production.

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Chloro- and Hydrido Complexes of (Pentamethylcyclopentadienyl) bis(phosphine)ruthenium ((펜타메틸시클로펜타디에닐) 비스(포스핀)루테늄의 염화물과 수소화물 유도체)

  • Dong-Hwan Lee
    • Journal of the Korean Chemical Society
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    • v.36 no.2
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    • pp.248-254
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    • 1992
  • Bis(phosphine)ruthenium derivatives $({\eta}^5-C_5Me_5)RuCl(PR_3)_2(PR_3=PMe_3,\; PMe_2Ph,\;PEt_3,\;PMePh_2$, 1/2DPPE, 1/2DPPB) (2a${\sim}$2f) have been synthesized by the reaction of $[({\eta}^5-C_5Me_5)RuCl_2]_2$ (1) with excessive phosphine in ethanol. The reaction of complexes $({\eta}^5-C_5Me_5)Ru(PR_3)_2Cl\;with\;NaBH_4$ in ethanol gave the corresponding hydride complexes $({\eta}^5-C_5Me_5)Ru(PR_3)_2H (PR_3=PMe_3, PEt_3, PMePh_2$, 1/2 DPPE, 1/2DPPB) (3a${\sim}$3e). Chloride complexes (2a${\sim}$2f) and hydride complexes (3a${\sim}$3e) were isolated as crystals, which were characterized by IR, $^1H-NMR$ , and elemental analysis.

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The Structures of Dehydrated Fully $Ca^{2+}$-Exchanged Zeolite A and of Its iodine Sorption Complex (칼슘 이온으로 완전히 치환된 제올라이트 A의 탈수 구조와 칼슘 치환 제올라이트 A에 요오드가 흡착된 착물 구조)

  • Jang, Se-Bok;Han, Yong-Wook;Kim, Duk-Soo;Kim, Yang
    • Korean Journal of Crystallography
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    • v.1 no.2
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    • pp.76-83
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    • 1990
  • The structures of dehydrated fully Ca2+ _exchanged zeolite A (a: 12.2a3(2) A and of its iodine sorption complex (a=12.258(2) A) have been determined by single-crystal X-ray diffraction methods in the cubic space group. Pm3m at 21(1)℃.the structures were refined to final R(weighted) indices of 0.081 with 206 reflections and 0.084 with 173 reflections, respectively for which I>3 w (I). In each structure. six divalent cations are located on three different theefold axes associated with 6-ring oxygens. Dehydrated Ca2+_A sorbs ca. 6.0 diiodine molecules per unit cell at 80℃(vapor pressure of I: is ca. 14.3 Torr). Each iodine molecule makes a close approach. along its ahs to framework oxygen atom with I-I distance of 2.71(2) A, I-O distance of 3.32(3) k. and I-I-0=180℃. The result indicates that diiodine molecule forms charge transfer complex with framework oxygen.

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Association between PPARGC1A Genetic Polymorphisms and Type 2 Diabetes Mellitus in the Korean Population (한국인 대상의 PPARGC1A 유전적 다형성과 제2형 당뇨병과의 상관성)

  • Jin, Hyun-Seok;Park, Sangwook
    • Korean Journal of Clinical Laboratory Science
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    • v.53 no.1
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    • pp.81-87
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    • 2021
  • The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide. T2DM is one of the most common types of diabetes and is caused by increased insulin resistance and reduced insulin secretion. Peroxisome proliferator-activated receptor γ coactivator 1 alpha (PPARGC1A) is a master modulator of mitochondrial biogenesis and of gluconeogenesis in liver. In this study, we analyzed genetic polymorphisms of PPARGC1A gene in a middle-aged Korean population with T2DM. Using the genotype data of 736 T2DM cases and 4544 healthy controls obtained from the Korean Association Resource (KARE), we analyzed genetic correlations between single nucleotide polymorphisms (SNPs) of PPARGC1A and T2DM. Fifteen SNPs of PPARGC1A demonstrated a statistically significant association with T2DM. Of these, rs10212638 exhibited the strongest correlation with T2DM (P-value=0.015, OR=1.29, CI=1.05~1.59), and the minor G allele of PPARGC1A increased the risk of T2DM. This is the first study to report a significant association between genetic polymorphisms in PPARGC1A and T2DM and suggests that SNPs of PPARGC1A display genetic correlations to the etiology of T2DM.

Characterization of Anti-anti-idiotypic Antibodies (Ab3) Induced by Immunization of Anti-idiotypic Antibodies (Ab2) Mimicking Disialoganglioside GD2 (Disialoganglioside GD2의 Anti-idiotypic Antibody (Ab2)에 의해 유도된 Anti-anti-idiotypic Antibodies (Ab3)의 특성)

  • Park, Yoon-Sun
    • IMMUNE NETWORK
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    • v.3 no.2
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    • pp.118-125
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    • 2003
  • Background: Disialoganglioside GD2 is a tumor-associated antigen that is overexpressed on tumor cells of neuroectodermal origin, such as melanoma and neuroblastoma. Anti-idiotypic antibodies that mimic GD2 may induce more effective immune responses than GD2 antigen itself, because they are protein antigens and are known to be able to break immune tolerance. In this study, to explore the potential of anti-idiotypic antibodies as tumor vaccines, the ability of anti-idiotypic antibodies (Ab2) to induce anti-anti-idiotypic antibodies (Ab3) that bind to the original antigen GD2 was investigated. Methods: Six monoclonal anti-idiotypic antibodies (1A8, 1G5, 2B6, 3A4, 3D6, 3H9) to monoclonal antibody M2058, which is a monoclonal antibody to GD2, were produced in mice. Three (1A8, 3A4, 3H9) of them were selected based on their ability to inhibit the binding of Ab1 to D142.34 (murine melanoma cell expressing GD2). These 3 different Ab2 were injected into rabbits, and rabbit Ab3 induced by each of them were characterized. Results: Ab3-containing sera from two rabbits immunized with 1A8, 3A4, or 3H9 bound significantly (P<0.05) to D142.34 but not to B78.96 (GD2-negative cell), and bound significantly (P<0.05) to isolated GD2 but not to GD1a. Ab3-containing sera from two rabbits immunized with 3A4 or 3H9 inhibited significantly (P<0.05) the binding of Ab1 M2058 to D142.34, and inhibited significantly (P<0.05) the binding of Ab1 M2058 to the Ab2. Conclusion: These results suggest that anti-idiotypic antibodies 3A4 and 3H9 have a potential to be used as vaccines against tumors expressing GD2 by inducing GD2-specific antibodies (Ab3).