赭曲霉素 | 4825-86-9

• 物质功能分类: 分析化学 - 标准品 - 食品和化妆品标准品
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 赭曲霉毒素及相关物质
• 中文名称: 赭曲霉素
• 中文别名: 赭曲毒素B；赭曲霉素B,来源于赭曲霉
• 英文名称: N-{[(3R)-8-hydroxy-3-methyl-1-oxo-3,4-dihydro-1H-isochromen-7-yl]-carbonyl}-L-phenylalanine
• 英文别名: N-{[(3R)-8-hydroxy-3-methyl-1-oxo-7-isochromanyl]carbonyl}-3-phenyl-L-alanine；ochratoxins B；ochratoxin A；ochratoxin B；OTB；(2S)-2-[[(3R)-8-hydroxy-3-methyl-1-oxo-3,4-dihydroisochromene-7-carbonyl]amino]-3-phenylpropanoic acid
• CAS: 4825-86-9
• 化学式: C₂₀H₁₉NO₆
• 分子量: 369.374
• InChiKey: DAEYIVCTQUFNTM-ABAIWWIYSA-N

物化性质

• 熔点：
  221° (van der Merwe)
• 比旋光度：
  D -35° (c = 0.15 in ethanol)
• 沸点：
  632.4±55.0 °C(Predicted)
• 密度：
  1.361±0.06 g/cm3(Predicted)
• 闪点：
  -11 °C
• 溶解度：
  DMF：10mg/mL； DMSO：15mg/mL；乙醇：50mg/mL；乙醇:PBS (pH 7.2) (1:1): 0.50 mg/ml
• 物理描述：
  Crystals that exhibit blue fluorescence. (NTP, 1992)
• 颜色/状态：
  Crystals from methanol
• 蒸汽压力：
  6.39X10-15 mm Hg at 25 °C (est)
• 旋光度：
  Specific optical rotation: -35 deg at 25 °C/D (concn = 0.15 in ethanol)
• 解离常数：
  pKa1 = 3.3 (carboxyl); pKa2 = 7.0 (hydroxyl) (est)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  113
• 氢给体数：
  3
• 氢受体数：
  6

ADMET

代谢

由于对OTB的生物转化了解甚少，本研究旨在探讨大鼠体内OTB的生物转化过程。雄性F344大鼠接受单次剂量的OTB（10 mg/kg体重）或多次剂量（2 mg/kg体重，每周5天，持续2周）的处理，并在最后一次给药后72小时处死。通过高效液相色谱（HPLC）结合荧光检测和液相色谱-串联质谱（LC-MS/MS）分析尿液和粪便中OTB及其代谢物的排泄情况。结果显示，OTB的主要代谢物是ochratoxin beta，这是由肽键断裂产生的，此外还有少量的4-羟基-OTB。在单次剂量给药后72小时内，总共有19%的给药剂量以OTB和ochratoxin beta的形式在尿液和粪便中被回收。与OTA不同，OTB在单次和多次给药后没有显示出明显的组织特异性保留。OTB比OTA更广泛地被代谢并且更快速地被消除。

... Since little is known regarding biotransformation ... of OTB, the aim of this study was to investigate biotransformation of OTB in rats... Male F344 rats were administered either a single dose of OTB (10 mg/kg bw) or repeated doses (2 mg/kg bw, 5 days/week for 2 weeks) and euthanized 72 hr after the last dosing. ... Excretion of OTB and metabolites in urine and feces was analyzed using both HPLC with fluorescence detection and LC-MS/MS. Ochratoxin beta, which results from cleavage of the peptide bond, was the major metabolite excreted in urine in addition to small amounts of 4-hydroxy-OTB. In total, 19% of the administered dose was recovered as OTB and ochratoxin beta in urine and feces within 72 hr after a single dose. In contrast to OTA, no tissue-specific retention of OTB was evident after single and repeated administration. ... OTB is more extensively metabolized and more rapidly eliminated than OTA. ...

来源:Hazardous Substances Data Bank (HSDB)

代谢

每天给猪喂食0.13毫克/千克体重的赭曲霉毒素B，连续8天后，赭曲霉毒素B被完全水解为赭曲霉毒素β。

Ochratoxin B (0.13 mg/kg body wt) fed to pigs daily for 8 days was completely hydrolyzed to ochratoxin beta.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在大鼠肝脏微粒体组分和NADPH的存在下，ochratoxin B形成了一种代谢产物。通过提取、薄层色谱、高压液相色谱和结晶，该产物从培养混合物中被分离出来。基于质谱和核磁共振光谱，推测其结构为4-羟基ochratoxin B。确定了形成4-羟基ochratoxin B的Km值，并且ochratoxin B的存在并不改变ochratoxin A的羟基化。大鼠通过腹腔注射ochratoxin A或B，或两者的混合物。在ochratoxin B存在的情况下，尿液中排出的三种代谢物，ochratoxin A、(4R)-4-羟基ochratoxin A和ochratoxin alpha的比例没有变化。Ochratoxin B被代谢为4-羟基ochratoxin B和ochratoxin beta，但与ochratoxin A代谢物的比例不同。当通过腹腔注射时，ochratoxin beta在24小时内被排出。单独使用ochratoxin A处理的大鼠，食物摄入量减少了50%，在近端小管中观察到严重的病变、变性和坏死。当ochratoxin A和B联合给药时，动物临床上未受影响，组织学上只有近端小管的轻微损伤。这些观察结果表明ochratoxin B显著减少了ochratoxin A的毒性作用。

A metabolic product was formed from ochratoxin B by rat liver microsomal fractions in the presence of NADPH. It was isolated from the incubation mixture by extraction, thin-layer chromatography, high-pressure liquid chromatography, and crystallization. On the basis of mass and nuclear magnetic resonance spectroscopy, the structure is suggested to be 4-hydroxyochratoxin B. The Km for the formation of 4-hydroxyochratoxin B was determined, and the hydroxylation of ochratoxin A was not altered by the presence of ochratoxin B. Rats were given ochratoxin A or B, or a mixture of both intraperitoneally. The ratios of the three metabolites, ochratoxin A, (4R)-4-hydroxyochratoxin A, and ochratoxin alpha, excreted in the urine did not change in the presence of ochratoxin B. Ochratoxin B was metabolized to 4-hydroxyochratoxin B and ochratoxin beta, but in a different ratio than for the ochratoxin A metabolites. When given intraperitoneally, ochratoxin beta was excreted within 24 hr. In rats treated with ochratoxin A alone, the food intake was reduced by 50%, and histologically severe lesions, degeneration, and necrosis were observed in the proximal tubules. When ochratoxin A and B given in combination, the animals were clinically unaffected and histologically there was only slight damage of proximal tubules. These observations indicate that ochratoxin B considerably reduces the toxic effects of ochratoxin A.

来源:Hazardous Substances Data Bank (HSDB)

代谢

这项研究的目标是开发和评估用于确认赭曲霉毒素A（OA）、开环赭曲霉毒素A（OP-OA）、赭曲霉毒素B（OB）、羟基赭曲霉毒素A（OA-OH）和赭曲霉毒素α（Oalpha）及其在大鼠体内由这些毒素形成的代谢物的程序，并证明在大鼠注射不同赭曲霉毒素后，可以在胆汁和尿液中识别出许多赭曲霉毒素代谢物。在酸化甲醇中的酯化程序和强碱中的内酯水解程序产生了大多数不同赭曲霉毒素的另外两种形式。酯化程序为确认赭曲霉毒素提供了一种简单、快速且可靠的方法。在大鼠的尿液和胆汁中检测到OA、OP-OA、OB、OA-OH和Oalpha的20种不同代谢物，其中几种被鉴定出来。在这些代谢物中，当注射OA或最近发现的具有毒性的OA形式（OP-OA）时，它们在体内很容易形成。本研究开发的程序可以用于确认和分离生物样本中的赭曲霉毒素，并表明除了OA和相关的赭曲霉毒素在体内形成了新的OA形式（OP-OA）之外，还形成了许多其他代谢物。

The objectives of this study were to develop and evaluate procedures for the confirmation of ochratoxin A (OA), lactone opened OA (OP-OA), ochratoxin B (OB), hydroxy OA (OA-OH) and ochratoxin alpha (Oalpha) and metabolites formed in the rats from these toxins, and to demonstrate that many ochratoxin metabolites can be identified in the bile and urine of rats injected with the different ochratoxins. An esterification procedure in acidified methanol and a lactone hydrolysis procedure in strong base yielded two additional forms of most of the different ochratoxins. The esterification procedure provided a simple, fast and reliable method for the confirmation of the ochratoxins. A total of 20 different metabolites of OA, OP-OA, OB, OA-OH and Oalpha were detected in the urine and the bile of rats of which several were identified. Among these, OA and the recently discovered and toxic form of OA (OP-OA) were readily formed in vivo when either were injected. Procedures developed in this study can be used to confirm and isolate ochratoxins in biological samples and have shown that a new form of OA (OP-OA) along with many other metabolites are formed from OA and related ochratoxins in vivo.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 副作用

职业性肝毒素 - 第二性肝毒素：在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒案例。

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中和。如果患者停止呼吸，请开始人工呼吸，最好使用需求阀复苏器、球囊阀面罩设备或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果患者呕吐，让患者向前倾或将其置于左侧（如果可能的话，头部向下），以保持呼吸道畅通，防止吸入。保持患者安静，维持正常体温。寻求医疗帮助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，用0.9%的生理盐水（NS）持续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。考虑使用药物治疗肺水肿……。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇……。监测心率和必要时治疗心律失常……。开始静脉输注D5W /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸林格氏液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象……。使用地西泮或劳拉西泮治疗癫痫……。使用丙美卡因氢氯化物协助眼部冲洗……。 /Poisons A and B/

/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

遗传毒性/为了阐明三种结构相关的真菌毒素，即赭曲霉毒素A（OTA）、赭曲霉毒素B（OTB）和桔霉素（CIT）对人类健康的影响，研究了它们在人类肝脏细胞系（HepG2）中的急性毒性、促有丝分裂性和遗传毒性效应。这些化合物在引起肾脏疾病的流行区的霉变食品中发现，与尿路癌症有关。与以前的实验一致，研究人员发现OTA在单细胞凝胶电泳（SCGE）试验中以剂量依赖性方式诱导微核（MN）和DNA迁移，在浓度大于或等于5微克/毫升时具有统计学意义。相比之下，OTB在相同条件下没有遗传毒性活性，但该化合物即使在低于OTA的剂量（10微克/毫升）下也引起了明显的细胞分裂抑制。CIT在MN试验中引起与OTA相似的效果（在剂量水平大于或等于2.5微克/毫升时显著），但在SCGE试验中为阴性。所有化合物在添加HepG2来源的酶匀浆（S9混合物）后，在TA98和TA100菌株的沙门氏菌/微粒体试验中未能诱导突变。通过使用DNA-着丝粒探针，研究人员发现OTA诱导的MN涉及染色体断裂效应（55-60%的MN为着丝粒阴性），而CIT诱导的MN主要是着丝粒阳性（78-82%）。这些发现表明OTB在人类衍生细胞中不具有遗传毒性活性，因此可能不是人类的遗传毒性致癌物。相比之下，CIT在HepG2细胞中是诱导MN的同等有效剂，但这种效果是由不同的机制引起的，即非整倍体。

/GENOTOXICITY/ To elucidate the effects of three structurally related mycotoxins, namely, ochratoxin A (OTA), ochratoxin B (OTB), and citrinin (CIT), on human health, ...their acute toxic, mitogenic, and genotoxic effects in the human-derived liver cell line (HepG2) /were investigated/. These compounds are found in moldy foods in endemic areas of nephropathy, which is associated with urinary tract cancers. In agreement with previous experiments, /investigators/ found that OTA causes a dose-dependent induction of micronuclei (MN) and DNA migration in the single-cell gel electrophoresis (SCGE) assay, which was statistically significant at concentrations of > or =5 ug/mL. In contrast, OTB was devoid of genotoxic activity under identical conditions, but the compound caused pronounced inhibition of cell division even at doses lower than OTA (10 ug/mL). CIT caused an effect similar to that of OTA in MN assays (significant at dose levels of > or =2.5 ug/mL) but was negative in the SCGE test. All compounds failed to induce mutations in Salmonella/microsome assays in strains TA98 and TA100 after addition of HepG2-derived enzyme homogenate (S9-mix). By use of DNA-centromeric probes /investigators/ found that induction of MN by OTA involves chromosome breaking effects (55-60% of the MN were centromere negative), whereas CIT-induced MN were predominantly centromere positive (78-82%). /These/ findings indicate that OTB is devoid of genotoxic activity in human-derived cells and therefore probably not a genotoxic carcinogen in humans. In contrast, CIT was an equally potent inducer of MN in HepG2 cells as OTA, but this effect is caused by a different mechanism, namely, aneuploidy.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

描述了标记性赭曲霉毒素A和B的制备方法。标记性赭曲霉毒素B的制备方法涉及通过混合酐合成赭曲霉毒素β的叠氮化物，然后与标记的苯丙氨酸进行偶联，以产生(14)C-赭曲霉毒素B。将标记的赭曲霉毒素注射到雄性Wistar大鼠中，在不同的存活时间后处死，并进行全身自动放射性造影。赭曲霉毒素A在大鼠体内的分布模式与之前在鼠标体内记录的模式没有差异。因此，大鼠（而不是小鼠）对赭曲霉毒素A诱导癌症的高度易感性不能通过毒素在特定细胞或器官的积累来解释。赭曲霉毒素A和B的分布模式几乎一致——唯一明显的区别是标记的赭曲霉毒素A在血液中的保留时间比赭曲霉毒素B长得多，后者更快地被排出。当分析组织提取物以寻找标记性代谢物时，只有注射了赭曲霉毒素B的大鼠的提取物被发现含有易于检测的浓度，而赭曲霉毒素A的代谢物未见。

Methods for preparation of labelled ochratoxin A and B are described. The method for preparation of labelled ochratoxin B involves the synthesis of the azide of ochratoxin beta via the mixed anhydride and subsequent conjugation to labelled phenylalanine to yield (14)C-ochratoxin B. The labelled ochratoxins were injected into male Wistar rats and after different survival times they were sacrificed and subjected to whole body autoradiography. The distribution pattern of ochratoxin A in the rat did not differ from that earlier registered for mouse. The previously known, high susceptibility of rats (and not mice) to ochratoxin A-induced cancer could thus not be explained by an accumulation of the toxin in specific cells or organs. The distribution patterns of ochratoxin A and B were almost congruent--the only apparent difference being a much longer retention of the labelled ochratoxin A in the blood compared to ochratoxin B, which was much faster excreted. When analyzing tissue extracts for labelled metabolites only the extracts from the rats injected with ochratoxin B were found to contain easily detectable concentrations, while no metabolites of ochratoxin A were seen.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

A和B混合物（0.38和0.13毫克/千克体重）在怀孕早期每天喂给猪8天。B型 ochratoxin吸收不良，在肠道中优先水解。

Mixture of ochratoxins A and B (0.38 and 0.13 mg/kg body wt) was fed to pigs daily for 8 days during early pregnancy. Ochratoxin B was poorly absorbed and preferentially hydrolyzed in intestinal tract.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

由于对OTB的生物转化了解甚少，本研究旨在探讨大鼠体内OTB的生物转化过程。雄性F344大鼠接受单次剂量的OTB（10 mg/kg体重）或重复剂量（2 mg/kg体重，每周5天，持续2周）给药，并在最后一次给药后72小时处死。使用高效液相色谱（HPLC）结合荧光检测和液相色谱-串联质谱（LC-MS/MS）分析尿液和粪便中OTB及其代谢物的排泄情况。结果显示，OTB的主要代谢物是ochratoxin beta，这是由肽键断裂产生的，此外还有少量的4-羟基-OTB。在单次给药后72小时内，尿液和粪便中回收了相当于给药剂量的19%的OTB和ochratoxin beta。与OTA不同，OTB在单次和重复给药后没有明显的特定组织保留。OTB比OTA更广泛地被代谢并且更快速地被消除。

... Since little is known regarding biotransformation ... of OTB, the aim of this study was to investigate biotransformation of OTB in rats... Male F344 rats were administered either a single dose of OTB (10 mg/kg bw) or repeated doses (2 mg/kg bw, 5 days/week for 2 weeks) and euthanized 72 hr after the last dosing. ... Excretion of OTB and metabolites in urine and feces was analyzed using both HPLC with fluorescence detection and LC-MS/MS. Ochratoxin beta, which results from cleavage of the peptide bond, was the major metabolite excreted in urine in addition to small amounts of 4-hydroxy-OTB. In total, 19% of the administered dose was recovered as OTB and ochratoxin beta in urine and feces within 72 hr after a single dose. In contrast to OTA, no tissue-specific retention of OTB was evident after single and repeated administration. ... OTB is more extensively metabolized and more rapidly eliminated than OTA. ...

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(a)
• 危险品标志：
  Xn,F,T
• 安全说明：
  S16,S26,S36,S45,S53
• 危险类别码：
  R36/38,R36/37/38,R22,R45,R48/23/24/25,R11,R65,R46
• WGK Germany：
  2,3
• 海关编码：
  39229000
• 危险类别：
  6.1(a)
• 危险品运输编号：
  UN 3462 6.1/PG 3

制备方法与用途

生物活性

Ochratoxin B 是由 Aspergillus ochraceus 产生的次级代谢产物，是一种无氯的霉菌毒素 Ochratoxin A 的类似物。研究表明，Ochratoxin B 能够降低 Ochratoxin A 的毒性作用，并且是啮齿动物中已知最有效的肾脏致癌物质之一。

类别

有毒物质

毒性分级

高毒

急性毒性

口服-鸡 LD50: 54 毫克/公斤

可燃性危险特性

可燃，燃烧时分解产生有毒的氮氧化物和氯化物气体

储运特性

应存放在低温、通风且干燥的地方；与食品原料分开存放

灭火剂

水、二氧化碳、干粉、砂土

反应信息

• 作为反应物：
  描述：

  赭曲霉素 在 甲醇 、 sodium hydroxide 作用下， 反应 24.0h， 生成
  参考文献：
  名称：

  Identification of ochratoxins and some of their metabolites in bile and urine of rats

  摘要：

  The objectives of this study were to develop and evaluate procedures for the confirmation of ochratoxin A (OA), lactone opened OA (OP-OA), ochratoxin B (OB), hydroxy OA (OA-OH) and ochratoxin alpha (O alpha) and metabolites formed in the rats from these toxins, and to demonstrate that many ochratoxin metabolites can he identified in the bile and urine of rats injected with the different ochratoxins. An esterification procedure in acidified methanol and a lactone hydrolysis procedure in strong base yielded two additional forms of most of the different ochratoxins. The esterification procedure provided a simple, fast and reliable method for the confirmation of the ochratoxins. A total of 20 different metabolites of OA, OP-OA, OB, OA-OH and O alpha were detected in the urine and the bile of rats of which several were identified. Among these, OA and the recently discovered and toxic form of OA (OP-OA) were readily formed in vivo when either were injected. Procedures developed in this study can be used to confirm and isolate ochratoxins in biological samples and hare shown that a new form of OA (OP-OA) along with many other metabolites are formed from OA and related ochratoxins in vivo. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0278-6915(99)00153-2
• 作为产物：
  描述：

  赭曲霉毒素A 在 葡萄糖 、 水 作用下， 反应 0.08h， 以20%的产率得到赭曲霉素
  参考文献：
  名称：

  Ochratoxin A acts as a photoactivatable DNA cleaving agent

  摘要：

  赭曲霉毒素A通过光诱导产生DNA断裂的能力被描述；在DNA存在的情况下，光反应产生非氯化的衍生物赭曲霉毒素B，而在无氧条件下则生成氢醌衍生物。

  DOI：

  10.1039/a708275d

文献信息

• Ochratoxin A Forms a Carbon-Bonded C8-Deoxyguanosine Nucleoside Adduct:  Implications for C8 Reactivity by a Phenolic Radical
  作者：Jian Dai、Marcus W. Wright、Richard A. Manderville

  DOI：10.1021/ja034221r

  日期：2003.4.1

  oxidation to yield phenoxyl radicals. The C8 position of dG is susceptible to radical attack, as was amply proven through formation of the hydroxyl radical-derived DNA lesion, 8-oxodeoxyguanosine. The adduct 4 is the first structurally characterized nucleoside adduct of a chlorophenolic toxin, and its formation has important implications for the mutagenicity of phenolic xenobiotics.

  已使用电喷雾质谱和核磁共振评估了致癌真菌毒素赭曲霉毒素 A (OTA, 1) 与脱氧鸟苷 (dG) 反应的能力。在 50 mol 当量 dG 存在下对 OTA (100 muM) 进行光激发，导致分离和鉴定 C8-脱氧鸟苷核苷加合物 4。重要的是，使用辣根过氧化物酶 (HRP)/ OTA 氧化活化后形成了相同的加合物H2O2 或过渡金属 Fe(II) 和 Cu(II)，如质谱所证实。因为人们认为 OTA 的致突变性和随后的致癌性源于氧化性 DNA 损伤（链断裂和氧化碱基产物）和鸟嘌呤特异性 DNA 加合物的形成，加合物 4 证实了 OTA 与 dG 共价反应的能力，并且对 OTA 和其他经过氧化产生苯氧基自由基的氯酚毒素的作用机制具有重要意义。dG 的 C8 位置易受自由基攻击，这一点已通过羟基自由基衍生的 DNA 损伤 8-氧代脱氧鸟苷的形成得到充分证明。加合物 4 是第一个具有结构特征
• COMPOUNDS AND COMPOSITIONS USEFUL IN THE TREATMENT OF NEOPLASIA
  申请人：McClay Allen

  公开号：US20090047221A1

  公开（公告）日：2009-02-19

  There is described compounds for use in therapy, said compounds being defined by Formula (1): There is also described an anti-proliferative composition comprising one or more compounds according to Formula (1), and a method of treatment of neoplasia comprising the administration of such a compound or composition.

  本文描述了用于治疗的化合物，该化合物由公式（1）定义：还描述了一种抗增殖组合物，其中包括一个或多个符合公式（1）的化合物，以及一种治疗肿瘤的方法，包括给予这样的化合物或组合物。
• Method of disinfecting a foodstuff using gaseous ozone
  申请人：L'AIR LIQUIDE, SOCIETE ANONYME POUR L'ETUDE ET L'EXPLOITATION DES PROCEDES GEORGES CLAUDE

  公开号：EP0988800A1

  公开（公告）日：2000-03-29

  The present invention provides a method of disinfecting a foodstuff using a gaseous mixture containing ozone in an amount and for a time sufficient to effect disinfection.

  本发明提供了一种使用含有臭氧的气体混合物对食品进行消毒的方法，臭氧的量和时间足以达到消毒效果。
• Method for producing purified and/or concentrated analytes, use and kit
  申请人：AOKIN AG

  公开号：EP2026068A1

  公开（公告）日：2009-02-18

  The present invention relates to a method for producing purified and/or concentrated analytes of interest from a sample of biological sources, said method comprising or consisting of the following steps: a) providing an affinity column capable of being centrifuged, the column comprising or consisting of: (i) a centrifugation column, (ii) optionally one, two or more separators, and (iii) an affinity matrix comprising a matrix and one or more, the same or different binding moieties, wherein the binding moieties are attached to the matrix in such a way, that the binding moieties are capable of binding to the analytes of interest to form a binding moiety-analyte-complex so that the analytes of interest are not eluted from the column, b) optionally washing the affinity column with a washing solvent, c) adding the sample comprising the analytes of interest to and filtering the sample through the affinity column, so that at least part of the analytes of interest of the sample form the binding moiety-analyte-complex, d) optionally washing the affinity column comprising the binding moiety-analyte-complexes with a washing solvent, e) adding an incubating solvent to said affinity column comprising the binding moiety-analyte-complexes, f) incubating the incubation solvent on the affinity column comprising the binding moiety-analyte-complexes, so that at least part of the binding moiety-analyte-complexes are destroyed and g) eluting the analytes of interest from the affinity column by way centrifugation, a use of an affinity column capable for being centrifuged, a kit comprising an affinity column and an affinity column.

  本发明涉及一种从生物源样品中制备纯化和/或浓缩的相关分析物的方法，所述方法包括或由以下步骤组成： a) 提供可离心的亲和柱，该亲和柱包括或由以下部分组成： (i) 离心柱、 (ii) 可选的一个、两个或多个分离器，以及 (iii) 由基质和一个或多个相同或不同的结合分子组成的亲和基质，其中结合分子以这样 的方式附着在基质上，即结合分子能够与感兴趣的分析物结合形成结合分子-分析物-复合物， 从而使感兴趣的分析物不会从柱中洗脱出来、 b) 用洗涤溶剂清洗亲和柱、 c) 将包含相关分析物的样品加入亲和柱并通过亲和柱过滤样品，使样品中的至少一部分相关分析物形成结合莫伊--分析物--络合物、 d) 选择性地用洗涤溶剂清洗亲和柱，亲和柱中包括结合莫伊-分析物-复合物、 e) 将孵育溶剂加入到所述亲和柱中，亲和柱中包含结合莫伊-分析物络合物、 f) 在亲和柱上孵育孵育溶剂，使至少部分结合莫伊耶-分析物复合物被破坏，以及 g) 通过离心从亲和柱中洗脱出感兴趣的分析物、 使用可离心的亲和柱、包括亲和柱和亲和柱的试剂盒。
• Method of determining a concentration of analytes of interest in a sample
  申请人：Aokin AG

  公开号：EP2048500A1

  公开（公告）日：2009-04-15

  Summary: The present invention relates to a method of determining a concentration of analytes of interest in a sample reaction mixture, which includes or is suspected to include the analytes of interest, comprising or consisting of the following steps: a) Measuring or providing intensities of the polarized fluorescence of one, two, three, four, five or more comparative reaction mixtures with differing concentrations of analytes of interest in vertical and horizontal direction over a given time period of the reaction, b) Measuring an intensity of the polarized fluorescence of a sample reaction mixture in vertical and horizontal direction over a given time period of the reaction, c) Determining preliminary concentrations of the analytes of interest in the sample reaction mixture by comparing the measured intensities of the sample reaction mixture at two, three, four, five or more time points of the reaction (tn = t0s + xn) with the intensities of the first, second, third, fourth, fifth and further comparative reaction mixture at the same time points of the reaction (tn = t0c + xn), d) Determining the margin of error for the preliminary concentration of the analytes of interest in the sample reaction mixture in step c) at the given time points (tn) and e) Determining the concentration of the analytes of interest in the sample reaction mixture by comparing the preliminary concentrations and the respective margin of error at the given time points (tn) and selecting the appropriate preliminary concentration or a mean value of preliminary concentrations to be the concentration of analytes of interest in the sample reaction mixture.

  摘要： 本发明涉及一种确定样品反应混合物中相关分析物浓度的方法，该混合物包括或疑似包括相关分析物，该方法包括或由以下步骤组成： a) 在反应的给定时间段内，测量或提供一种、两种、三种、四种、五种或更多种具有不同浓度的相关分析物的比较反应混合物在垂直和水平方向上的偏振荧光强度、 b) 在反应的给定时间段内，测量样品反应混合物在垂直和水平方向上的偏振荧光强度、 c) 将样品反应混合物在反应的两个、三个、四个、五个或更多时间点（tn = t0s + xn）的测量强度与第一、第二、第三、第四、第五和更多比较反应混合物在反应的相同时间点（tn = t0c + xn）的强度进行比较，确定样品反应混合物中相关分析物的初步浓度、 d) 在给定的时间点（tn），确定步骤 c）中样品反应混合物中相关分析物初步浓度的误差范围，以及 e) 通过比较给定时间点（tn）的初步浓度和各自的误差范围，确定样品反应混合物中相关分析物的浓度，并选择适当的初步浓度或初步浓度的平均值作为样品反应混合物中相关分析物的浓度。