Anatoxin-a and homoanatoxin-a are potent neurotoxins produced by cyanobacteria such as Oscillatoria PCC 6506. Sequencing of the genome of this strain is underway, and ... a 29 kb DNA fragment containing a sequence called ks2 t... previously shown to be specific to Oscillatoria cyanobacteria producing anatoxin-a and homoanatoxin-a /was identified/. Bioinformatic analysis of this 29 kb fragment revealed a cluster of genes, which were annotated. The function assigned to the products of eight contiguous genes, from anaA to anaH, provides a clue to the biosynthesis of anatoxin-a and homoanatoxin-a. Proline is first loaded on an acyl carrier protein and its five-membered cycle oxidized to the pyrroline oxidation state. This activated ring is then successively loaded on three polyketide synthase modules for elongation, reduction, cyclization, and methylation. The final step is the hydrolysis of the thioester with subsequent decarboxylation. GC-MS and NMR analyses of homoanatoxin-a produced by PCC 6506 using labeled precursors confirm that proline is very likely the starter of these polyketide synthases. ... Specific PCR amplifications ... showed that the anaC, anaE, anaF, and anaG genes are always present in the genome of cyanobacteria producing anatoxin-a and homoanatoxin-a and absent in nonproducing strains. Histidine-tagged AnaC was purified to homogeneity and showed to catalyze the loading of proline on purified histidine-tagged AnaD that had been previously transformed into its holo form using the Bacillus subtilis Sfp phosphopantetheinyl transferase. All of these data provide strong evidence that ... the gene cluster responsible for the production of anatoxin-a and homoanatoxin-a in Oscillatoria PCC 6506 /has been identified/.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
毒性总结
识别和使用：鱼毒素A是一种油。鱼毒素A是由几种淡水蓝藻产生的一种神经毒素，与家畜和野生动物的致命中毒有关。人体研究：一名青少年在充满有毒蓝藻膜的池塘中摔跤和潜水后，因暴露于蓝绿色藻类毒素而死亡。蓝藻细胞在粪便样本中被发现，毒素在藻膜样本中被测量到。这名青少年和他的朋友都出现了严重的呕吐、腹泻和腹痛。在受影响较严重的人身上，这种情况在暴露后48小时以休克和抽搐告终。涉嫌的毒素鱼毒素A是一种快速作用的神经毒素，但没有关于人类接触的数据。虽然神经毒素可能会引起死亡，通过呼吸抑制和抽搐，但它不会预期会导致胃肠炎。动物研究：鱼毒素A是由几种蓝藻属产生的一种强效神经毒素。有报道称，野生动物和家畜因接触鱼毒素A而死亡，这是由神经肌肉接头处乙酰胆碱受体的抑制驱动的有毒反应。随后的神经元去极化导致肌肉细胞过度刺激。在怀孕的第12至14天（器官形成后），每天一次或三次，分别以200或125微克/千克体重的剂量给仓鼠腹腔注射鱼毒素A，在第15天处死母鼠。每天三次的治疗导致所有10窝胎儿中有1窝胎儿畸形（脑积水），几乎所有的胎儿都生长迟缓。每天一次的治疗导致生长迟缓。没有观察到母体毒性。鱼毒素A在小鼠睾丸中引起了剂量依赖性的组织病理学变化，如精子管的变性、精原细胞线的细胞间分离、精母细胞在管腔中的脱落、Sertoli细胞的空泡化和精母细胞的丢失。对Salmonella typhimurium TA 1535/pSK1002菌株进行了遗传毒性测试，包括代谢转化和不包括代谢转化。毒素浓度分别为0.25、0.5、1和2微克/毫升。没有代谢转化时，鱼毒素A的最高无效浓度为0.25微克/毫升。在有代谢激活的情况下没有检测到效果。1990年和1991年，狗在饮用苏格兰因什湖沿岸含有底栖蓝藻水华的水后死亡。受影响动物的中毒迹象和实验室生物测试中水华提取物的极高神经毒性表明，这是由蓝藻神经毒素引起的急性中毒。神经毒性水华主要由底栖Oscillatoria物种组成，这些物种也在中毒狗的胃内容物中被观察到。胃内容物在生物测试中也是神经毒性的，其症状与Oscillatoria水华相同。蓝藻生物碱神经毒素鱼毒素A在水华提取物和中毒狗的胃内容物中被鉴定出来。生态毒性研究：1985年，在加拿大艾伯塔省埃德蒙顿北部约150公里处的一个湖中观察到蝙蝠大量死亡。超过1000只Myotis spp.和灰蝙蝠（Lasiurus cinereus）因饮用湖中的水而死于"藻类中毒"。蓝藻水华被怀疑是丹麦湖泊在1993年7月和1994年6-7月期间鸟类死亡的原因。鱼毒素A是鱼类免疫细胞的凋亡诱导剂。将17期和25期的蟾蜍胚胎（Bufo arenarum）暴露于0.03-30.0毫克/升的鱼毒素A，持续10天。不良影响包括剂量依赖性的短暂中枢神经系统抑制、水肿和失去平衡。最值得注意的是，在高剂量下，两组在暴露后6-13天都出现了100%的死亡率。
IDENTIFICATION AND USE: Anatoxin A is an oil. Anatoxin A is a neurotoxin produced by several freshwater cyanobacteria and implicated in lethal poisonings of domesticated animals and wildlife. HUMAN STUDIES: Teenager who had been wrestling and diving in a pond with a heavy scum of toxic Anabaena flos-aquae died through exposure to blue-green algal toxin. The cyanobacterial cells were found in fecal samples, and toxin was measured in scum samples. The teenager and his friend both suffered severe vomiting, diarrhea, and abdominal pain. In the more severely affected individual, this ended in shock and seizure 48 hr after exposure. The toxin implicated, anatoxin A, is a fast-acting neurotoxin, but there are no data on human exposure. A neurotoxin would not be expected to cause the gastroenteritis, though it could cause death through respiratory inhibition and convulsions. ANIMAL STUDIES: Anatoxin A is a potent neurotoxin produced by several genera of cyanobacteria. Deaths of wild and domestic animals due to anatoxin-a exposure have been reported following a toxic response that is driven by the inhibition of the acetylcholine receptors at neuromuscular junctions. The consequent neuron depolarization results in an overstimulation of the muscle cells. Doses of 200 or 125 ug/kg bw anatoxin A were given i.p. to hamsters one or three times per day, respectively, at days 12 to 14 of pregnancy (after organogenesis), and the dams were sacrificed at day 15. The treatment given three times per day caused fetal malformation (hydrocephaly) in all fetuses in one of 10 litters, and stunted growth in almost all litters. Treatment given once per day resulted in stunted growth. No maternal toxicity was observed. Anatoxin A caused dose-dependent histopathological changes in the testes of mice such as degenerations in seminiferous tubules, intercellular disassociation of spermatogenetic cell lines, sloughing of germ cells into tubular lumen, vacuolization in Sertoli cells and loss of germ cells. Genotoxicity test was conducted on Salmonella typhimurium TA 1535/pSK1002 strain, with and without metabolic transformation. The toxin concentrations were 0.25, 0.5, 1 and 2 ug/mL. The highest inefficient concentration of anatoxin A without metabolic transformation was 0.25 ug/m. No effects were detected with metabolic activation. Dog deaths occurred in 1990 and 1991 after the animals drank water containing blooms of benthic cyanobacteria along the shoreline of Loch Insh, Scotland. Signs of poisoning in the affected animals and the high neurotoxicity of bloom extracts in laboratory bioassays indicated acute poisoning due to cyanobacterial neurotoxin(s). The neurotoxic blooms consisted largely of benthic Oscillatoria species which were also observed in the stomach contents of the poisoned dogs. Stomach contents were also neurotoxic in bioassays with the same signs of poisoning as the Oscillatoria blooms. The cyanobacterial alkaloid neurotoxin anatoxin A was identified in bloom extracts and poisoned dog stomach contents. ECOTOXICITY STUDIES: A die-off of bats was observed in a lake about 150 km north of Edmonton, Alberta, Canada, in 1985. Over 1000 Myotis spp. and hoary bats (Lasiurus cinereus) died of 'algal poisoning' caused by an alkaloid when they drank water from the lake. Cyanobacterial blooms were implicated in bird kills at lakes in Denmark in July 1993 and June-July 1994. Anatoxin A is an inducer of apoptosis in fish immune cells. Stages 17 and 25 toad embryos (Bufo arenarum) were exposed to 0.03-30.0 mg/L of anatoxin-a for 10 days. Adverse effects included a dose-dependent transient CNS depression, edema and loss of equilibrium. Most notable was the occurrence of 100% mortality at the high dose in both groups 6-13 days post-exposure.
Some 2000 species of cyanobacteria (blue-green algae) occur globally in aquatic habitats. They are able to survive under a wide range of environmental conditions and some produce potent toxins. Toxin production is correlated with periods of rapid growth (blooms) and 25%-70% of blooms may be toxic. Anatoxin-a is an alkaloid neurotoxin that acts as a potent neuro-muscular blocking agent at the nicotinic receptor. Acute toxicity, following consumption of contaminated water, is characterized by rapid onset of paralysis, tremors, convulsions and death. Human exposures may occur from recreational water activities and dietary supplements, but are primarily through drinking water. The current studies were conducted to examine the effect of in utero exposure on postnatal viability, growth and neurodevelopment, to evaluate the potential of in vitro embryotoxicity, and to explore the synergistic relationship between anatoxin-a and the algal toxin microcystin-LR by the oral route. The results of preliminary studies on amphibian toxicity are also reported. Time-pregnant mice received 125 or 200 ug/kg anatoxin-a by intraperitoneal injection on gestation days (GD) 8-12 or 13-17. Pup viability and weight were monitored over a 6-day period. Maternal toxicity (decreased motor activity) was observed at 200 ug/kg in both treatment periods. There were no significant treatment-related effects on pup viability or weight on postnatal day (PND) 1 or 6. The GD 13-17 pups were evaluated on PND 6, 12 and 20 for standard markers of neurodevelopmental maturation (righting reflex, negative geotaxis and hanging grip time). No significant postnatal neurotoxicity was observed. In vitro developmental toxicity was evaluated in GD 8 mouse embryos exposed to 0.1-25 um anatoxin-a for 26-28 hr. Perturbations in mouse yolk sac vasculature were noted from the 1.0 um concentration in the absence of significant embryonic dysmorphology. Potential algal toxin synergism was tested in mice receiving either 0, 500 or 1,000 ug/kg microcystin-LR by gavage and approximately 50 min later receiving either 0, 500, 1,000 or 2,500 ug/kg anatoxin-a by the same route. No deaths occurred at any dose and no definitive signs of intoxication were observed. Stages 17 and 25 toad embryos (Bufo arenarum) were exposed to 0.03-30.0 mg/L of anatoxin-a for 10 days. Adverse effects included a dose-dependent transient narcosis, edema and loss of equilibrium. Most notable was the occurrence of 100% mortality at the high dose in both groups 6-13 days post-exposure. The observed delay between initial exposure and death is highly unusual for anatoxin-a.
VET: There is no specific antidote for anatoxin-a. Because of the rapid onset of clinical signs, emesis is not likely to be useful. Although there are no studies that evaluate the efficacy of specific decontamination procedures, administration of activated charcoal has been recommended. In addition, artificial respiration may be of benefit along with general supportive care. Specific measures to control seizures include benzodiazepines, phenobarbital or pentobarbital. If given, they may cause central nervous system (CNS) and respiratory depression and careful monitoring of the animal is necessary. In any seizuring animal, control of body temperature is an important part of the symptomatic care.
/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 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/
/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/
[EN] COMPOUNDS FOR FAST AND EFFICIENT CLICK RELEASE<br/>[FR] COMPOSÉS POUR LIBÉRATION DE CHIMIE CLICK RAPIDE ET EFFICACE
申请人：TAGWORKS PHARMACEUTICALS B V
公开号：WO2020256546A1
公开（公告）日：2020-12-24
The invention disclosed herein relates to compounds, combinations, kits, and methods using same, for use in bioorthogonal release reactions. In particular, the compounds, combinations and kits of the invention can be used to achieve fast and efficient click release. Applications of the compounds, combinations, and kits of the invention include both in vitro and in vivo applications.
[EN] TETRAZINES FOR HIGH CLICK RELEASE SPEED AND YIELD<br/>[FR] TÉTRAZINES POUR UNE VITESSE ET UN RENDEMENT DE LIBÉRATION DE CHIMIE CLIC ÉLEVÉS
申请人：TAGWORKS PHARMACEUTICALS B V
公开号：WO2020256544A1
公开（公告）日：2020-12-24
Disclosed herein are tetrazines substituted with groups that result in a high click conjugation yield and high click release yields. In some of several other aspects, the invention relates to combinations and kits comprising said tetrazines and a dienophile, preferably a trans-cyclooctene. In another aspect, the compounds, combinations, and kits are for use as a medicament.
[EN] AGENTS FOR CLEAVING LABELS FROM BIOMOLECULES IN VIVO<br/>[FR] AGENTS PERMETTANT DE CLIVER IN VIVO DES MARQUEURS LIÉS À DES BIOMOLÉCULES
申请人：TAGWORKS PHARMACEUTICALS B V
公开号：WO2020256545A1
公开（公告）日：2020-12-24
Disclosed herein are compounds comprising trans-cyclooctene moieties, combinations, and kits that can be used to more quickly remove radionuclides from a subject, preferably a human being. Said compounds, combinations and kits can also be used to increase the tumor-to-blood ratio, or to more rapidly and/or conveniently achieve such an increase, of a label in targeted imaging or targeted radiotherapy in a subject, preferably a human being.
A short and enantioselective synthesis of (+)-Anatoxin-a
作者：Peter Somfai、Jens Åhman
DOI：10.1016/0040-4039(92)80026-g
日期：1992.6
A short and enantioselective total synthesis of the neurotoxicalkaloid (+)-Anatoxin-a (1) from the L-pyroglutamic acid derivative 2 is described. The key step involves an intramolecular cyclisation of an N-tosyl iminium ion derived from the corresponding α-methoxy sulfonamide.
Disclosed are multibinding compounds which are muscarinic receptor antagonists. The multibinding compounds of this invention containing from 2 to 10 ligands covalently attached to one or more linkers. Each ligand is, independently of each other, a muscarinic receptor antagonist or an allosteric modulator provided that at least one of said ligand is a muscarinic receptor antagonist. The multibinding compounds of this invention are useful in the treatment and prevention of diseases such as chronic obstructive pulmonary disease, chronic bronchitis, irritable bowel syndrome, urinary incontinence, and the like.
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