Coclaurine
(Synonyms: 衡州乌药碱,(+)-(R)-Coclaurine; (R)-Coclaurine; d-Coclaurine) 目录号 : GC61477
A benzylisoquinoline alkaloid with nAChR inhibitory and insecticidal activities
Cas No.:486-39-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Coclaurine is a benzylisoquinoline alkaloid that has been found in T. quinquenervia and has nicotinic acetylcholine receptor (nAChR) inhibitory and insecticidal activities.1,2 It inhibits ACh-induced currents in Xenopus oocytes expressing human α4β2 or α4β4 subunit-containing nAChRs (IC50s = 49 and 18 ?M, respectively).1 Coclaurine induces mortality in D. melanogaster and C. pomonella larvae (LD50s = 78.2 and 35.4 ?g/ml, respectively).2
1.Exley, R., Iturriaga-Vásquez, P., Lukas, R.J., et al.Evaluation of benzyltetrahydroisoquinolines as ligands for neuronal nicotinic acetylcholine receptorsBr. J. Pharmacol.146(1)15-24(2005) 2.Quiroz-Carre?o, S., Pastene-Navarrete, E., Espinoza-Pinochet, C., et al.Assessment of insecticidal activity of benzylisoquinoline alkaloids from Chilean Rhamnaceae plants against fruit-fly Drosophila melanogaster and the lepidopteran crop pest Cydia pomonellaMolecules25(21)5094(2020)
| Cas No. | 486-39-5 | SDF | |
| 别名 | 衡州乌药碱,(+)-(R)-Coclaurine; (R)-Coclaurine; d-Coclaurine | ||
| Canonical SMILES | OC1=CC2=C(C=C1OC)CCN[C@H]2CC3=CC=C(O)C=C3 | ||
| 分子式 | C17H19NO3 | 分子量 | 285.34 |
| 溶解度 | DMSO : 25 mg/mL (87.61 mM; ultrasonic and warming and heat to 60°C) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.5046 mL | 17.523 mL | 35.0459 mL |
| 5 mM | 0.7009 mL | 3.5046 mL | 7.0092 mL |
| 10 mM | 0.3505 mL | 1.7523 mL | 3.5046 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Structure and Biocatalytic Scope of Coclaurine N-Methyltransferase
Angew Chem Int Ed Engl 2018 Aug 13;57(33):10600-10604.PMID:29791083DOI:10.1002/anie.201805060.
Benzylisoquinoline alkaloids (BIAs) are a structurally diverse family of plant secondary metabolites, which have been exploited to develop analgesics, antibiotics, antitumor agents, and other therapeutic agents. Biosynthesis of BIAs proceeds via a common pathway from tyrosine to (S)-reticulene at which point the pathway diverges. Coclaurine N-methyltransferase (CNMT) is a key enzyme in the pathway to (S)-reticulene, installing the N-methyl substituent that is essential for the bioactivity of many BIAs. In this paper, we describe the first crystal structure of CNMT which, along with mutagenesis studies, defines the enzymes active site architecture. The specificity of CNMT was also explored with a range of natural and synthetic substrates as well as co-factor analogues. Knowledge from this study could be used to generate improved CNMT variants required to produce BIAs or synthetic derivatives.
Determination of higenamine and Coclaurine levels in human urine after the administration of a throat lozenge containing Nandina domestica fruit
Drug Test Anal 2017 Nov;9(11-12):1788-1793.PMID:28801989DOI:10.1002/dta.2258.
Higenamine is a key component of traditional Chinese herbal medicine. The fruit of Nandina domestica (which contains this component) is available as an ingredient in the so-called Nanten-nodo-ame throat lozenge found on the Japanese market, which is an over-the-counter pharmaceutical and is easy to purchase for Japanese athletes. However, higenamine is a non-selective β2-agonist, which is exemplified in the prohibited list of the World Anti-Doping Agency (WADA). Therefore, some have raised a concern regarding the potential cause of increased unintentional higenamine doping cases in the Asian region. This study aimed to investigate components of throat lozenges and develop a mass-spectrometry method for the quantification of higenamine and Coclaurine in human urine. Moreover, a population study of Japanese subjects (n = 246) and an excretion study (n = 4) of the corresponding throat-lozenge recipients were performed to test the applicability of the current reporting threshold (i.e., 10 ng/mL) of higenamine set by WADA. The estimates of higenamine and Coclaurine were 2.2 ± 0.1 μg/drop (mean of n = 12) and 0.5 ± 0.01 μg/drop (mean of n = 12), respectively. The maximum concentrations of higenamine and Coclaurine were 0.2-0.4 and 0.3-1.0 ng/mL, respectively, at 10-12 h after administration of higenamine (nine drops); however, the concentrations in all four volunteers did not reach the positivity criterion of 10 ng/mL. No higenamine and Coclaurine could be detected in the Japanese subjects. Therefore, there is no risk of detecting unintentional higenamine doping when the WADA reporting threshold is used.
In silico identification and structure function analysis of a putative Coclaurine N-methyltransferase from Aristolochia fimbriata
Comput Biol Chem 2020 Apr;85:107201.PMID:31986303DOI:10.1016/j.compbiolchem.2020.107201.
In this study we isolated and performed in silico analysis of a putative Coclaurine N-methyltransferase (CNMT) from the basal angiosperm Aristolochia fimbriata. The Aristolochiaceae plant family produces alkaloids similar to the Papavaraceae family, and CNMTs are central enzymes in biosynthesis pathways producing compounds of ethnopharmacological interest. We used bioinformatics and computational tools to predict a three-dimensional homology model and to investigate the putative function of the protein and its mechanism for methylation. The putative CNMT is a unique (S)-adenosyl-L-methionine (SAM)-dependent N-methyltransferase, catalyzing transfer of a methyl group from SAM to the amino group of Coclaurine. The model revealed a mixed α/β structure comprising seven twisted β-strands surrounded by twelve α-helices. Sequence comparisons and the model indicate an N-terminal catalytic Core domain and a C-terminal domain, of which the latter forms a pocket for Coclaurine. An additional binding pocket for SAM is connected to the Coclaurine binding pocket by a small opening. CNMT activity is proposed to follow an SN2-type mechanism as observed for a similarly conformed enzyme. Residues predicted for the methyl transfer reaction are Tyr79 and Glu96, which are conserved in the sequence from A. fimbriata and in homologous N-methyltransferases. The isolated CNMT is the first to be investigated from any basal angiosperm.
Purification and characterization of Coclaurine N-methyltransferase from cultured Coptis japonica cells
Phytochemistry 2001 Apr;56(7):649-55.PMID:11314949DOI:10.1016/s0031-9422(00)00481-7.
S-Adenosyl-L-methionine (SAM): Coclaurine N-methyltransferase (CNMT), which catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to the amino group of the tetrahydrobenzylisoquinoline alkaloid Coclaurine. was purified 340-fold from Coptis japonica cells in 1% yield to give an almost homogeneous protein. The purified enzyme, which occurred as a homotetramer with a native Mr of 160 kDa (gel-filtration chromatography) and a subunit Mr of 45 kDa (SDS-polyacrylamide gel electrophoresis), had an optimum pH of 7.0 and a pI of 4.2. Whereas (R)-coclaurine was the best substrate for enzyme activity, Coptis CNMT had broad substrate specificity and no stereospecificity CNMT methylated norlaudanosoline, 6,7-dimethoxyl-1,2,3,4-tetrahydroisoquinoline and 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline. The enzyme did not require any metal ion. p-Chloromercuribenzoate and iodoacetamide did not inhibit CNMT activity, but the addition of Co2+, Cu2+ or Mn2+ at 5 mM severely inhibited such activity by 75, 47 and 57%, respectively. The substrate-saturation kinetics of CNMT for norreticuline and SAM were of the typical Michaelis-Menten-type with respective Km values of 0.38 and 0.65 mM.
In vivo bioconversion of tetrahydroisoquinoline by recombinant Coclaurine N-methyltransferase
Biosci Biotechnol Biochem 2004 Apr;68(4):939-41.PMID:15118328DOI:10.1271/bbb.68.939.
Coclaurine N-methyltransferase from Coptis japonica catalyzes the N-methylation of Coclaurine as well as simple tetrahydroisoquinoline. We examined the possibility of converting 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline into its N-methylated product using transgenic Escherichia coli, which expressed recombinant Coclaurine N-methyltransferase, without the addition of a methyl-group donor. Transgenic E. coli successfully N-methylated the substrate added to the medium and excreted the product. Limitation of bioconversion by the supply of methyl-group donor is discussed.