• 제목/요약/키워드: ligand

검색결과 2,327건 처리시간 0.027초

울금의 주요 성분인 커큐민과 나노 마이셀링 기법 적용 염화 커큐민의 트랜스타이레틴 활성 부위에 대한 결합 친화도 비교분석 (Molecular Docking Affinity Comparison of Curcumin and Nano-micelled Curcumin with Natural Sea Salt on Transthyretin)

  • 김동찬;송표
    • 생명과학회지
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    • 제26권2호
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    • pp.253-258
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    • 2016
  • 본 연구에서는 울금의 주요 성분인 커큐민과 나노 마이셀링 기법을 적용한 신규 조성물인 염화 커큐민(NMC)의 트랜스타이레틴(TTR) 단백질 활성 부위에 대한 in silico 분자 결합 친화도를 비교 분석하였다. 우선 NMC신규 조성물의 결정학적 구조를 광학 및 전자현미경을 활용하여 관찰하였을 때, 나노 마이셀링 적용 NMC 결정은 일반 천일염에 비하여 색상 및 질감이 전체적으로 균일화 되었고, 천일염과 NMC성분이 강하게 일체화되어 기간이 상당히 경과 되더라도 쉽게 분리가 되지 않는 고기능성 안전성 구조물이 형성되었다. TTR단백질의 3차원 구조 활성 부위에 대한 in silico 분자 결합 친화도는 NMC가 일반 커큐민에 비하여 상대적으로 높은 결합 친화도를 나타나었고, pharmacophore 모델링 분석에서도 NMC가 일반 커큐민에 비하여 TTR 활성 부위에서 현저하게 pharmacophore 각도의 차이가 나타났었으며 패턴 또한 밀집된 특징을 나타내었다. 결론적으로, 나노 마이셀링 적용 NMC가 일반 커큐민에 비하여 상대적으로 우수하게 TTR 단백질의 활성 부위에 결합하는 것을 확인하였고, 이는 TTR 활성에 의해 유도되는 질병 조절 물질로의 적용 가능성이 있다고 판단된다. 결론적으로 일반 커큐민과 같은 생리 활성 효능 성분에 나노 마이셀링 기법을 적용하므로서 효율적인 결합 타깃 단백질 활발 조절 및 이러한 성분을 활용한 기능성 식품 산업에 나노 마이셀링 기법을 효율적으로 적용할 수 있음을 확인하였다.

중합촉매 시스템이 폴리페닐렌에테르의 합성에 미치는 영향 (The Effects of Polymerization Catalyst Systems on the Synthesis of Poly(2,6-dimethyl-1,4-phenylene ether))

  • 이창재;김용태;김진규;김지흥;남성우;전붕수;김영준
    • 폴리머
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    • 제36권1호
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    • pp.98-103
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    • 2012
  • 구리 계열의 $Cu(NO_2)_2{\cdot}3H_2O$와 CuCl을 중합촉매로 사용하고 다양한 용매, 리간드와 염기의 함량을 변화시켜 poly(2,6-dimethyl-1,4-phenylene ether)(PPE) 중합반응을 고찰하였다. 이 가운데 CuCl/1-methylimidazole/ammonium hydroxide 시스템에서 가장 높은 중합 수율을 나타내었다. 한편, 몇 가지 다른 유기용매와 메탄올의 혼합용매 시스템에서 용매의 성분비율을 변화시켜 용매의 조성이 중합반응에 미치는 영향을 조사하였으며 2,4,6-trimethylphenol (TMP)를 사용하여 TMP 함량에 따른 분자량 조절 효과를 조사하였다. 클로로포름/메탄올 9/1(v/v) 혼합용매를 사용했을 때 가장 높은 중합 수율과 높은 분자량을 갖는 중합체($\overline{M_n}$ : 55 K; $\overline{M_w}$ : 92 K; PDI: 1.7)를 얻었다. 구리 일가 촉매인 CuCl 과 CuI를 사용하여 서로다른 짝이온, 즉 $Ci^-$$I^-$ 이온이 중합결과에 미치는 영향을 조사하였다. 촉매의 활성 비교를 위하여 산소 흡수량(oxygen-uptake)을 측정하였으며, 중합반응의 부산물인 5,5'-tetramethyl-4,4'-diphenoquinone (DPQ)의 함량을 자외선 분광기(ultraviolet spectroscopy)를 통하여 분석하였다.

Anomalous Luminescence and Emission Quenching Behaviors of Tris(2,2$^\prime$-bipyridine)Ruthenium(Ⅱ) in Poly(methacrylic acid) Solutions$^1$

  • Park, Joon-Woo;Paik, Young-Hee
    • Bulletin of the Korean Chemical Society
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    • 제7권2호
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    • pp.137-142
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    • 1986
  • The luminescence spectra of $Ru(bpy)_3^{2+}$ in poly(methacrylic acid) (PMA) solutions varied sensitively with pH. At pH < 5.5, the emission intensity increased with pH up to 4 times, while it decreased with pH beyond the pH. The enhanced emission intensity was accompanied by blue-shift of the emission maxima as much as 15 nm. The enhancement of emission intensity was attributed to the restricted rotational mobility of ligand of the cation bound to densely coiled PMA molecules at pH < 5.5. The sharp decrease in emission intensity with increasing pH near pH 5.6 was accounted for conformational transition of the polymer to more extended structure, which was also revealed in viscosity measurement. The enhancement of emission intensity became higher as NaCl concentration of the solution increased. The binding constant of $Ru(bpy)_3^{2+}$ with two carboxylate groups of PMA was calculated as $2{\times}10^5\;M^{-1}$ in 0.1 M NaCl at pH 5.2. The pH dependence of luminescence quenching rate of $Ru(bpy)_3^{2+}$ by $Cu^{++}$ also showed maximum near pH 5, and the rate was more than $10^3$ times higher than that in water, whereas the maximum enhancement of quenching rate (about 20 times) in poly(acrylic acid) (PAA) solution occurred at pH 4.5. On the other hand, the pH dependence for neutral water soluble nitrobenzene (NB) exhibited opposite trend to that of $Cu^{++}$. The quenching constant vs pH curve for $MV^{++}$ was composite of those for $Cu^{++}$ and NB. The anomalous high quenching rate for $Cu^{++}$ in PMA solution at pH < 5.5 was attributed to the binding of $Ru(bpy)_3^{2+}$ and $Cu^{++}$ to the same region of PMA, when it conforms densely coiled structure in the pH range. The observation of mininium quenching rate for NB near pH 5.5 indicated that the $Ru(bpy)_3^{2+}$ bound to the densely coiled PMA is not accessible by NB, which is in bulk water phase. The composite nature of the pH dependence of quenching rate for $MV^{++}$ in PMA solution was attributed to the smaller binding affinity of the cation to PMA, compared to that of $Cu^{++}$. The sharp, cooperative conformational transition with pH observed in PMA was not revealed in PAA. But, the pH dependence of quenching rates in this polymer reflected increased charge density and, thus, binding of cations to the polymer, and expansion of the polymer chain with pH.

Whole genome MBD-seq and RRBS analyses reveal that hypermethylation of gastrointestinal hormone receptors is associated with gastric carcinogenesis

  • Kim, Hee-Jin;Kang, Tae-Wook;Haam, Keeok;Kim, Mirang;Kim, Seon-Kyu;Kim, Seon-Young;Lee, Sang-Il;Song, Kyu-Sang;Jeong, Hyun-Yong;Kim, Yong Sung
    • Experimental and Molecular Medicine
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    • 제50권12호
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    • pp.1.1-1.14
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    • 2018
  • DNA methylation is a regulatory mechanism in epigenetics that is frequently altered during human carcinogenesis. To detect critical methylation events associated with gastric cancer (GC), we compared three DNA methylomes from gastric mucosa (GM), intestinal metaplasia (IM), and gastric tumor (GT) cells that were microscopically dissected from an intestinal-type early gastric cancer (EGC) using methylated DNA binding domain sequencing (MBD-seq) and reduced representation bisulfite sequencing (RRBS) analysis. In this study, we focused on differentially methylated promoters (DMPs) that could be directly associated with gene expression. We detected 2,761 and 677 DMPs between the GT and GM by MBD-seq and RRBS, respectively, and for a total of 3,035 DMPs. Then, 514 (17%) of all DMPs were detected in the IM genome, which is a precancer of GC, supporting that some DMPs might represent an early event in gastric carcinogenesis. A pathway analysis of all DMPs demonstrated that 59 G protein-coupled receptor (GPCR) genes linked to the hypermethylated DMPs were significantly enriched in a neuroactive ligand-receptor interaction pathway. Furthermore, among the 59 GPCRs, six GI hormone receptor genes (NPY1R, PPYR1, PTGDR, PTGER2, PTGER3, and SSTR2) that play an inhibitory role in the secretion of gastrin or gastric acid were selected and validated as potential biomarkers for the diagnosis or prognosis of GC patients in two cohorts. These data suggest that the loss of function of gastrointestinal (GI) hormone receptors by promoter methylation may lead to gastric carcinogenesis because gastrin and gastric acid have been known to play a role in cell differentiation and carcinogenesis in the GI tract.

Interaction of the Post-transition Metal Ions and New Macrocycles in Solution

  • Jung, Oh-Jin
    • Bulletin of the Korean Chemical Society
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    • 제14권6호
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    • pp.687-691
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    • 1993
  • Complexation of $Cd^{2+},\;Pb^{2+}\;and\;Hg^{2+}$ ions with four cryptands were studied by potentiometry and solution calorimetry in various weight percent methanol-aqueous solvent at 25${\circ}$C under $CO_2$free nitrogen atmosphere. The stabilities of the complexes were dependent on the cavity size of macrocycles. The $Hg^{2+}$ ion stability constants are higher than those of $Cd^{2+}\;and\;Pb^{2+}$ ion. All the cryptands formed complexes having 1 : 1 (metal to ligand) mole-ratio except for $Hg^{2+}-L_1$ (cryptand 1,2b: 3,5-benzo-9,14,17-trioxa-1,7-diazabicyclo-(8,5,5) heptadecane) and $Cd^{2+}-L_2$ (cryptand 2,2b: 3,5-benzo-10,13,18,21-tetraoxa-1,7-diazabicyclo (8,5,5) eicosane) complexes. $Hg^{2+}-L_1$ complex was a sandwitch type, and the $Cd^{2+}-L_2$ complex showed two stepwise reactions. Thermodynamic parameters of the $Cd^{2+}-L_2$ complex were $6.08(log\;K_1)$, -7.28 Kcal/mol $({\Delta}H_1)$, and $4.78\;(log\;K_2)$, -4.62 Kcal/mol $({\Delta}H_2)$, respectively, for 1 : 1 and 2: 1 mole-ratio. The sequences of the selectivity were increased in the order of $Hg^{2+}\;>Pb^{2+}\;>Cd^{2+}$ ion for $L_3\;and\;L_4$ macrocycles, and the $L_2$-macrocycle has a selectivity for $Cd^{2+}$ ion relative to $Zn^{2+},\;Ni^{2+},\;Pb^{2+}\;and\;Hg^{2+}$ ions. Thus, it is expected that the $L_2$ can be used as carrier for seperation of the post transition metals by macrocycles-mediated liquid membrane because $L_2$ is not soluble in water, and the difference of stability constants of the metal complexes with $L_2$ are large as compared with the other transition metal complexes. The $^1H\;and\;^{13}C-NMR studies indicated that the nitrogen atoms of cryptands have greater affinity to the post transition metal ions than the oxygen atoms, and that the planarities of the macrocycles were lost by complexation with the metal ions because of the perturbation of ring current of benzene molecule attached to macrocycles and counter-anions.

Selective Dimerization and Cyclotrimerization of Phenylacetylene with Rhodium and Iridium Complexes

  • Chin, Chong-Shik;Won, Gyong-Shik;Song, Joong-Ho
    • Bulletin of the Korean Chemical Society
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    • 제15권11호
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    • pp.961-966
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    • 1994
  • Oligomerization of phenylacetylene is catalyzed by $Rh(ClO_4)(CO)(PPh_3)_2$ (Rh-1), $[Rh(CO)(PPh_3)_3]ClO_4$ (Rh-2), $[Rh(COD)L_2]ClO_4 (L_2=(PPh_3)_2$, Rh-3; $(PPh_3)(PhCN)$, Rh-4; $(PhCN)_2$, Rh-5), $[Rh(C_3H_5)(Cl)(CO)(SbPh_3)_2]ClO_4$ (Rh-6), $[Ir(COD)L_2]ClO_4 (L_2=(PPh_3)_2$, $Ir-1; (PPh_3)(PhCN)$, $Ir-2; (PhCN)_2$, Ir-3; (AsPh_3)(PhCN)$, $Ir-4; Ph_2PCH_2CH_2PPh_2$, Ir-5; COD, Ir-6 and 2,2'-dipyridyl, Ir-7), $Ir(ClO_4)(CO)(PPh_3)_2$, $Ir-8, [Ir(PhCN)(CO)(PPh_3)_2]ClO_4$, Ir-9 to produce dimerization products, 1,3-diphenylbut-1-yn-3-ene, 1, (E)-1,4-diphenylbut-1-yn-3-ene, 2 and (Z)-1,4-diphenylbut-1-yn-3-ene, 3, and cyclotrimerization products, 1,3,5-triphenylbenzene, 4 and 1,2,4-triphenylbenzene, 5. Product distribution of the oligomers varies depending on various factors such as the nature of catalysts, reaction temperature, counter anions and excess ligand present in the reaction mixtures. Increasing reaction temperature in general increases the yield of the cyclotrimerization products. Exclusive production of dimer 1 and trimer 4 can be obtained with Ir-1 at 0 $^{\circ}$C and with Ir-2 in the presence of excess PhCN (or $CH_3CN$) at 50 $^{\circ}$C, respectively. Dimer 2 (up to 81%) and trimer 5 (up to 98%) are selectively produced with Rh-1 at 50 and 100 $^{\circ}$C respectively. Production of 3 is selectively increased up to 85% by using $PF_6$- salt of $[Ir(COD)(PPh_3)_2]$+ at 25 $^{\circ}$C. Addition of $CH_3I$ to Rh-1 produces $CH_3PPh_3^+I-$ and increases the rate of oligomerization(disappearance of phenylacetylene). Among the metal compounds investigated in this study, Ir-1 catalyzes most rapidly the oligomerization where the catalytically active species seems to contain lr(PPh3)2 moiety. The stoichiometric reaction of phenylacetylene wth Ir-9 at 25 $^{\circ}$C quantitatively produces hydridophenyl-ethynyl iridium(III) complex, $[lr(H)(C{\equiv}CPh)(PhCN)(CO)(PPh_3)_2]ClO_4$ (Ir-11), which seems to be an intermediate for the oligomerization.

Effects of Gintonin-enriched fraction on the gene expression of six lysophosphatidic receptor subtypes

  • Lee, Rami;Lee, Byung-Hwan;Choi, Sun-Hye;Cho, Yeon-Jin;Cho, Han-Sung;Kim, Hyoung-Chun;Rhim, Hyewhon;Cho, Ik-Hyun;Rhee, Man Hee;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • 제45권5호
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    • pp.583-590
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    • 2021
  • Background: Gintonin, isolated from ginseng, acts as a ginseng-derived lysophosphatidic acid (LPA) receptor ligand and elicits the [Ca2+]i transient through six LPA receptor subtypes (LPARSs). However, the long-term effects of gintonin-enriched fraction (GEF) on the gene expression of six LPARSs remain unknown. We examined changes in the gene expression of six LPA receptors in the mouse whole brain, heart, lungs, liver, kidneys, spleen, small intestine, colon, and testis after long-term oral GEF administration. Methods: C57BL/6 mice were divided into two groups: control vehicle and GEF (100 mg/kg, p.o.). After 21-day saline or GEF treatment, total RNA was extracted from nine mouse organs. Quantitative-real-time PCR (qRT-PCR) and western blot were performed to quantify changes in the gene and protein expression of the six LPARSs, respectively. Results: qRT-PCR analysis before GEF treatment revealed that the LPA6 RS was predominant in all organs except the small intestine. The LPA2 RS was most abundant in the small intestine. Long-term GEF administration differentially regulated the six LPARSs. Upon GEF treatment, the LPA6 RS significantly increased in the liver, small intestine, colon, and testis but decreased in the whole brain, heart, lungs, and kidneys. Western blot analysis of the LPA6 RS confirmed the differential effects of GEF on LPA6 receptor protein levels in the whole brain, liver, small intestine, and testis. Conclusion: The LPA6 receptor was predominantly expressed in all nine organs examined; long-term oral GEF administration differentially regulated LPA3, LPA4, and LPA6 receptors in the whole brain, heart, lungs, liver, kidneys, small intestine, and testis.

Modern diagnostic capabilities of neonatal screening for primary immunodeficiencies in newborns

  • Khalturina, Evgenia Olegovna;Degtyareva, Natalia Dmitrievna;Bairashevskaia, Anastasiia Vasi'evna;Mulenkova, Alena Valerievna;Degtyareva, Anna Vladimirovna
    • Clinical and Experimental Pediatrics
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    • 제64권10호
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    • pp.504-510
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    • 2021
  • Population screening of newborns is an extremely important and informative diagnostic approach that allows early identification of babies who are predisposed to the development of a number of serious diseases. Some of these diseases are known and have effective treatment methods. Neonatal screening enables the early diagnosis and subsequent timely initiation of therapy. This helps to prevent serious complications and reduce the percentage of disability and deaths among newborns and young children. Primary immunodeficiency diseases and primary immunodeficiency syndrome (PIDS) are a heterogeneous group of diseases and conditions based on impaired immune system function associated with developmental defects and characterized by various combinations of recurrent infections, development of autoimmune and lymphoproliferative syndromes (genetic defects in apoptosis, gene mutation Fas receptor or ligand), granulomatous process, and malignant neoplasms. Most of these diseases manifest in infancy and lead to serious illness, disability, and high mortality rates. Until recently, it was impossible to identify children with PIDS before the onset of the first clinical symptoms, which are usually accompanied by complications in the form of severe coinfections of a viral-bacterial-fungal etiology. Modern advances in medical laboratory technology have allowed the identification of children with severe PIDS, manifested by T- and/or B-cell lymphopenia and other disorders of the immune system. This review discusses the main existing strategies and directions used in PIDS screening programs for newborns, including approaches to screening based on excision of T-cell receptors and kappa-recombination excision circles, as well as the potential role and place of next-generation sequencing technology to increase the diagnostic accuracy of these diseases.

주요 병원균 자극에 의한 닭의 Interleukin-34 발현 분석 비교 (Expression Analysis of Chicken Interleukin-34(IL-34) for Various Pathogenic Stimulations)

  • 홍영호
    • 한국가금학회지
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    • 제48권3호
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    • pp.111-122
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    • 2021
  • 최근에 IL-34가 MCSFR에 대한 두 번째 기능적 리간드로 확인되었으며, M-CSFR에 대한 결합을 통해 IL-34는 M-CSF와 유사한 기능을 공유한다. 지금까지 닭의 IL-34에 대한 실험적 연구가 아닌 예측된 서열로만 보고되었으며, 닭의 IL-34 기능에 대한 정보는 아직 부족하다. 닭 IL-34의 잠재적 생물학적 기능을 구명하기 위하여, 다양한 품종의 닭, 세포주에 대한 괴사성 장염, 살모넬라 및 E. coli 유래의 LPS 등을 처리하여 관찰하였다. 또한 닭의 IL-34와 M-CSF 재조합 단백질 생산 및 이를 이용한 전염증성 사이토카인 유도를 위하여 클로닝 및 재조합 단백질을 발현 및 정제하였다. 특히 관절이상 육계(unknown cause)에 대한 IL-34, M-CSF, 그리고 M-CSFR 유전자의 발현이 대조구보다 유의하게 증가하였으나, 병원균 자극 조직의 경우 많은 조직에서 감소함을 보였다. M-CSFR의 발현은 in vitro에서 IL-34와 M-CSF 재조합 단백질에 의해 증가함을 보였으며, IFN-γ은 재조합 단백질 M-CSF을 제외한 IL-34에 의해 증가하였다. 하지만, IL-12 발현은 유의적인 차이가 없었으며, IL-1β의 경우는 감소하였다. 이 결과는 IL-34와 M-CSF가 고전적인 대식세포와 대체 대식세포 모두에서 역할을 한다고 할 수 있다. 결론적으로, in vitro와 in vivo 실험을 통하여 병원균 처리 시 닭의 IL-34 발현을 관찰하였으며, IL-34 재조합 단백질이 대식세포에서와 전염증성과 항염증성 반응에 중요한 역할을 함을 증명하였다. 추후에 IL-34의 사이토카인, 케모카인 그리고 염증반응 경로 등에 대한 추가 연구가 필요하다고 판단된다.

Effect of ciglitazone on adipogenic transdifferentiation of bovine skeletal muscle satellite cells

  • Zhang, Junfang;Li, Qiang;Yan, Yan;Sun, Bin;Wang, Ying;Tang, Lin;Wang, Enze;Yu Jia;Nogoy, Kim Margarette Corpuz;Li, Xiangzi;Choi, Seong-Ho
    • Journal of Animal Science and Technology
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    • 제63권4호
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    • pp.934-953
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    • 2021
  • Ciglitazone is a member of the thiazolidinedione family, and specifically binds to peroxisome proliferator-activated receptor-γ (PPARγ), thereby promoting adipocyte differentiation. We hypothesized that ciglitazone as a PPARγ ligand in the absence of an adipocyte differentiation cocktail would increase adiponectin and adipogenic gene expression in bovine satellite cells (BSC). Muscle-derived BSCs were isolated from six, 18-month-old Yanbian Yellow Cattle. The BSC were cultured for 96 h in differentiation medium containing 5 µM ciglitazone (CL), 10 µM ciglitazone (CM), or 20 µM ciglitazone (CH). Control (CON) BSC were cultured only in a differentiation medium (containing 2% horse serum). The presence of myogenin, desmin, and paired box 7 (Pax7) proteins was confirmed in the BSC by immunofluorescence staining. The CL, CM, and CH treatments produced higher concentrations of triacylglycerol and lipid droplet accumulation in myotubes than those of the CON treatment. Ciglitazone treatments significantly increased the relative expression of PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα), C/EBPβ, fatty acid synthase, stearoyl-CoA desaturase, and perilipin 2. Ciglitazone treatments increased gene expression of Pax3 and Pax7 and decreased expression of myogenic differentiation-1, myogenin, myogenic regulatory factor-5, and myogenin-4 (p < 0.01). Adiponectin concentration caused by ciglitazone treatments was significantly greater than CON (p < 0.01). RNA sequencing showed that 281 differentially expressed genes (DEGs) were found in the treatments of ciglitazone. DEGs gene ontology (GO) analysis showed that the top 10 GO enrichment significantly changed the biological processes such as protein trimerization, negative regulation of cell proliferation, adipocytes differentiation, and cellular response to external stimulus. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that DEGs were involved in the p53 signaling pathway, PPAR signaling pathway, biosynthesis of amino acids, tumor necrosis factor signaling pathway, non-alcoholic fatty liver disease, PI3K-Akt signaling pathway, and Wnt signaling pathway. These results indicate that ciglitazone acts as PPARγ agonist, effectively increases the adiponectin concentration and adipogenic gene expression, and stimulates the conversion of BSC to adipocyte-like cells in the absence of adipocyte differentiation cocktail.