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一氧化氮(nitric oxide,NO)在肿瘤病理生理过程中产生多方面的生化作用,诸如引起的某些核苷酸碱基的羟基化,参与免疫系统清除肿瘤细胞,促进肿瘤细胞凋亡和调节血管生成等.在此基础上,首次提出将NO供体(NO donor)或一氧化氮合酶(nitric oxide synthase,NOS)抑制剂分别连接到甲氨蝶呤(methotrexate,MTX,MTX本身就是NOS抑制剂)的α或γ位羧基上的设想,设计并合成出:(1)MTX-NO供体(3-羟甲基-4-苯基-1,2,5-噁二唑-2-氧化物,属于Furoxan衍生物,缩写为FU):1a(MTX-α-FU),2a(MTX-γ-FU);(2)MTX-NOS抑制剂(L-N^ω-硝基精氨酸或L-N^ω-硝基精氨酸甲酯):1b(MTX-α-L-N^ω-NO2-Arg),2b(MTX-γ-L-N^ω-NO2-Arg),1c(MTX-α-L-N^ω-NO2-Arg-OMe),2c(MTX-γ-L-N^ω-NO2-Arg-OMe).在生物活性测试中,我们选择耐MTX细胞株K-562(慢性粒细胞性白血病急性病变细胞株),进行抗肿瘤活性测试,得到以下结果:(1)脂溶性差的MTX衍生物1b,2b抗肿瘤活性低于MTX,其它1a,2a;1c,2c均优于MTX;(2)连接有NO供体的MTX明显增强了MTX衍生物的抗肿瘤活性;(3)MTX中谷氨酸γ位组合物抗肿瘤活性均高于相应的α位异构体的活性.以上初步结果,将对进一步研究NO抗肿瘤作用以及新的抗肿瘤药物设计提供新的思路,对肿瘤临床化疗也有一定的参考价值. 相似文献
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将人的诱导型一氧化氮合成酶(hiNOS)启动子构建在带荧光素酶基因的载体pGL3-basic上, 构建成用荧光素酶为系统的启动子, 以研究载体p8.3iNOS. 结果显示, 肾母细胞肿瘤抑制因子(WT1)能够有效地抑制hiNOS启动子的转录; 且WT1的4个选择性剪接本的抑制效果有所不同, 其中WT1(-/-)在两种肝癌细胞(HepG2和Hep3B)中对hiNOS的表达均具有最强的抑制作用, 并且抑制效果具有剂量依赖性, 用Western blot检测结果进一步证实HepG2细胞中WT1(-/-)过量表达能下调hiNOS表达. 以上结果说明WT1在肝癌细胞中对人的hiNOS具有转录调节作用. 相似文献
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Miloš R. Filipović Dr. Alaric C. W. Koh Dr. Stéphane Arbault Dr. Vesna Niketić Dr. Andrea Debus Ulrike Schleicher Dr. Christian Bogdan Dr. Manon Guille Dr. Fréderic Lemaître Dr. Christian Amatore Dr. Ivana Ivanović‐Burmazović Dr. 《Angewandte Chemie (International ed. in English)》2010,49(25):4228-4232
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以机械混合法、浸渍法和共沉淀法分别制备了4%Ni-Al2O3催化剂,并用X射线衍射、程序升温还原、紫外-可见漫反射光谱和N2吸附等方法对催化剂的体相和表面结构进行了表征,系统考察了制备方法及焙烧温度对Ni-Al2O3催化剂催化丙烷选择性还原NO性能的影响. 结果表明, Ni-Al2O3中存在NiO和NiAl2O4两种镍相,前者是丙烷氧化活性中心,后者是NO选择性催化还原的活性中心. 共沉淀法制备的催化剂活性最好, 550 ℃焙烧的Ni-Al2O3催化剂在反应温度为450和500 ℃时NO转化率接近100%. 相似文献
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The use of nitric oxide (NO) is emerging as a promising, novel approach for the treatment of antibiotic resistant bacteria and biofilm infections. Depending on the concentration, NO can induce biofilm dispersal, increase bacteria susceptibility to antibiotic treatment, and induce cell damage or cell death via the formation of reactive oxygen or reactive nitrogen species. The use of NO is, however, limited by its reactivity, which can affect NO delivery to its target site and result in off-target effects. To overcome these issues, and enable spatial or temporal control over NO release, various strategies for the design of NO-releasing materials, including the incorporation of photo-activable, charge-switchable, or bacteria-targeting groups, have been developed. Other strategies have focused on increased NO storage and delivery by encapsulation or conjugation of NO donors within a single polymeric framework. This review compiles recent developments in NO drugs and NO-releasing materials designed for applications in antimicrobial or anti-biofilm treatment and discusses limitations and variability in biological responses in response to the use of NO for bacterial eradiation. 相似文献
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一氧化氮(NO)是一种普遍存在的生理信号分子,但利用NO作为触发方法来精细调节仿生聚合物的自组装行为的研究却很少.本工作报道一种独特的具有一氧化氮(NO)反应特性的新型pH响应双亲水性嵌段共聚物(doublehydrophilicblockcopolymer,DHBC),其中NO可以自发地触发聚(寡聚乙二醇甲醚甲基丙烯酸酯)-嵌段-聚(NO响应性基元-共-7-硝基苯并呋咱衍生物)(POEGMA-b-P(APUEMA-co-NBD))双亲水嵌段共聚物,分别在酸性和中性环境中发生自组装和形态转变.在引入荧光团之后,这些转变还可以和NO存在下光致诱导电子转移过程被阻断导致荧光增强相关联,从而提供了观察细胞内NO的机会. 相似文献
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《Analytical letters》2012,45(8):685-690
Abstract Standard mixtures of nitric oxide may be prepared by converting NO2 to NO in presence of a molybdenum catalyst. Quantitative conversion has been obtained in the concentration range 0–100 pnm at temperatures as low as 200°C. It has been proved that this material is scarcely affected by poisoning when exposed to high levels of nitrogen oxides. 相似文献
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Magdalena Wyszyska Monika Nitsze-Wierzba Aleksandra Czelakowska Jacek Kasperski Joanna ywiec Magorzata Skucha-Nowak 《Molecules (Basel, Switzerland)》2022,27(13)
The measurement of nitric oxide (NO) in exhaled air is used in diagnostics and monitoring the pathologies not only in the respiratory system but also in the oral cavity. It has shown a huge increase in its level in asthma and diseases of the oral cavity. It seems reasonable to undertake research on the impact of inflammation on the level of NO in exhaled air. The aim of the study is to make an evidence-based review of the application of NO levels in exhaled air in the diagnosis of inflammation and treatment monitoring on the basis of selected measuring devices. Methods and Results: This paper presents an example of the application of NO measurement in exhaled air in individual human systems. Selected measuring devices, their non-invasiveness, and their advantages are described. Discussion: The usefulness of this diagnostic method in pathologies of the oral cavity was noted. Conclusions: Measuring the level of NO in exhaled air seems to be a useful diagnostic method. 相似文献
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A general procedure for the synthesis of NG-alkyl, and NG-aryl-L -arginines with relatively high overall yield is reported. The key step involved the coupling of protected L -ornithine 4 with isothiourea 7 to give the fully protected NG-aryl-L -arginine derivative 8 . Subsequent deprotection of 8 in acidic condition provided the final target compound 9 with an overall yield of more than 80%. 相似文献
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Conversion of Nitric Oxide into Nitrous Oxide as Triggered by the Polarization of Coordinated NO by Hydrogen Bonding 下载免费PDF全文
Chuan‐Hung Chuang Prof. Wen‐Feng Liaw Prof. Chen‐Hsiung Hung 《Angewandte Chemie (International ed. in English)》2016,55(17):5190-5194
Reduction of the {Co(NO)}8 cobalt–nitrosyl N‐confused porphyrin (NCP) [Co(CTPPMe)(NO)] ( 1 ) produced electron‐rich {Co(NO)}9 [Co(CTPPMe)(NO)][Co(Cp*)2] ( 2 ), which was necessary for NO‐to‐N2O conversion. Complex 2 was NO‐reduction‐silent in neat THF, but was partially activated to a hydrogen‐bonded species 2 ??? MeOH in THF/MeOH (1:1, v/v). This species coupling with 2 transformed NO into N2O, which was fragmented from an [N2O2]‐bridging intermediate. An intense IR peak at 1622 cm?1 was ascribed to ν(NO) in an [N2O2]‐containing intermediate. Time–course ESI(?) mass spectra supported the presence of the dimeric [Co(NCP)]2(N2O2) intermediate. Five complete NO‐to‐N2O conversion cycles were possible without significant decay in the amount of N2O produced. 相似文献
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Roksana Markiewicz Jagoda Litowczenko Jacek Gapiski Anna Wo
niak Stefan Jurga Adam Patkowski 《Molecules (Basel, Switzerland)》2022,27(3)
Measurement of the nitric oxide (NO) concentration in living cells in the physiological nanomolar range is crucial in understanding NO biochemical functions, as well as in characterizing the efficiency and kinetics of NO delivery by NO-releasing drugs. Here, we show that fluorescence correlation spectroscopy (FCS) is perfectly suited for these purposes, due to its sensitivity, selectivity, and spatial resolution. Using the fluorescent indicators, diaminofluoresceins (DAFs), and FCS, we measured the NO concentrations in NO-producing living human primary endothelial cells, as well as NO delivery kinetics, by an external NO donor to the immortal human epithelial living cells. Due to the high spatial resolution of FCS, the NO concentration in different parts of the cells were also measured. The detection of nitric oxide by means of diaminofluoresceins is much more efficient and faster in living cells than in PBS solutions, even though the conversion to the fluorescent form is a multi-step reaction. 相似文献
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《Analytical letters》2012,45(11):2021-2036
Abstract Nitric oxide (NO) is now recognized as an important mediator that regulates a number of physiological functions. The most sensitive chemical method for its quantitation is via a redox-chemiluminescence detector (RCD), which can detect sub-picomole quantities of NO. In a microsomal metabolism study involving nitroglycerin, we observed that NH3 could produce a chemiluminescence signal that interfered with the assay of NO, although the RCD sensitivity toward NH3 was, on a molar basis, approximately 2700× less than that toward NO. Incorporation of a Porapak® T column either completely removed NH3 RCD signal (< 40 nmole), or caused a chromatographic separation between NH3 and NO (> 40 nmole of NH3). The presence of the polymer packing did not affect the sensitivity of detector response toward NO. The applicability of this separation method was validated in a biochemical study in which microsomes from bovine coronary artery smooth muscle cells were incubated under conditions that would produce NO as well as NH3 the latter probably through protein degradation. The separation method described appears to be useful in safeguarding artifactual contamination from NH3 in the redox chemiluminescence assay of NO. 相似文献
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Ricardo Corro Carlos Franco Urquijo Oscar Aguila Elisa Villa Jesus Santana Amelia Rios Bruno Escalante 《Molecules (Basel, Switzerland)》2022,27(21)
In the presence of a vascular thrombus, the recovery of blood flow and vascular recanalization are very important to prevent tissue damage. An alternative procedure to thrombolysis is required for patients who are unable to receive surgery or thrombolytic drugs due to other physical conditions. Recently, the performance of thrombolysis combined with microbubbles has become an attractive and effective therapeutic procedure. Indeed, in a recent study, we demonstrated that, upon exposure to ultrasound, liposomes loaded with nitric oxide release agonists conjugated to microbubbles; therefore, there is potential to release the agonist in a controlled manner into specific tissues. This means that the effect of the agonist is potentiated, decreasing interactions with other tissues, and reducing the dose required to induce nitric-oxide-dependent vasodilation. In the present study, we hypothesized that a liposome microbubble delivery system can be used as a hydrophilic agonist carrier for the nitric oxide donor spermine NONOate, to elicit femoral vasodilation and clot degradation. Therefore, we used spermine-NONOate-loaded microbubbles to evaluate the effect of ultrasound-mediated microbubble disruption (UMMD) on thromboembolic femoral artery recanalization. We prepared spermine NONOate-loaded microbubbles and tested their effect on ex vivo preparations, hypothesizing that ultrasound-induced microbubble disruption is associated with the vasorelaxation of aortic rings. Thrombolysis was demonstrated in aorta blood-flow recovery after disruption by spermine NONOate-loaded microbubbles via ultrasound application in the region where the thrombus is located. Our study provides an option for the clinical translation of NO donors to therapeutic applications. 相似文献
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Bansal S Gaspari M Raj HG Kumar A Cuda G Verheij E Tyagi YK Ponnan P Rastogi RC Parmar VS 《Applied biochemistry and biotechnology》2008,144(1):37-45
Our earlier investigations identified acetoxy drug: protein transacetylase (TAase), a unique enzyme in the endoplasmic reticulum
(ER) catalyzing the transfer of acetyl groups from polyphenolic acetates (PA) to certain functional proteins. Recently we
have established the identity of TAase with ER protein calreticulin (CR) and subsequently transacetylase function of CR was
termed calreticulin transacetylase (CRTAase). CRTAase was purified and characterized from human placenta. CRTAase catalyzed
the acetylation of a receptor protein nNOS, by a model PA 7, 8-diacetoxy-4-methylcoumarin (DAMC), which was visually confirmed
by using antiacetyl lysine. The aim of this report was to provide tacit proof by providing mass spectrometry evidence for
CRTAase catalyzed acetylation of purified nNOS by DAMC. For this purpose, purified nNOS was incubated with DAMC and CRTAase,
the modified nNOS was analyzed by nanoscale LC-MS/MS, which recorded 11 distinct peptides with a significant score as acetylated
on lysine residues. The distribution was in order: lysines-24, -33, -38, -131, and -229 of the PDZ domain, Lys-245 of the
oxygenase domain, Lys-754 and -856 of FMN binding domain, Lys-989 of connecting domain and Lys-1300, -1321, and -1371 of the
NADPH-binding domain were acetylated. The results documented in this paper highlighted for the first time modification of
nNOS by way of acetylation. Our earlier work recorded the profound activation of platelet NADPH cytochrome P-450 reductase
and the acetylation of the reductase protein by DAMC, which also remarkably enhanced intracellular levels of nitric oxide.
The results reported here coupled with the aforementioned previous observations strongly implicate the possible role of the
acetylation of the reductase domain of nitric oxide synthase (NOS) in the NOS activation. In addition, the acetylation of
nNOS can be expected to potentiate the interaction with CR, eventually leading to the augmented catalytic activity of NOS
and expression of the related biological effects. 相似文献