Toyocamycin (hydrate)
(Synonyms: NSC 63701, NSC 99843) 目录号 : GC48189
A natural antibiotic and IRE1α inhibitor
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
Toyocamycin is a natural adenosine analog first isolated from Streptomyces and shown in early studies to be cytotoxic to bacteria, fungi, and cancer cells and to have antiviral activities. Toyocamycin prevents IRE1α-induced mRNA cleavage (IC50 = 80 nM) and inhibits constitutive activation of XBP1 in multiple myeloma cell lines.1 It is used to study IRE1α action in the endoplasmic reticulum stress response, particularly in the context of cancer.2,3 It also inhibits phosphatidylinositol kinase in vitro (IC50 = 3.3 µg/ml), but not in cells, and blocks the ribosomal RNA-processing kinase Rio1 (IC50 = ~30 nM).4,5
1.Ri, M., Tashiro, E., Oikawa, D., et al.Identification of Toyocamycin, an agent cytotoxic for multiple myeloma cells, as a potent inhibitor of ER stress-induced XBP1 mRNA splicingBlood Cancer J.2(7)(2016) 2.Chien, W., Ding, L.W., Sun, Q.Y., et al.Selective inhibition of unfolded protein response induces apoptosis in pancreatic cancer cellsOncotarget5(13)4881-4894(2014) 3.Sun, H., Lin, D.C., Guo, X., et al.Inhibition of IRE1α-driven pro-survival pathways is a promising therapeutic application in acute myeloid leukemiaOncotarget7(14)18736-18749(2016) 4.Nishioka, H., Sawa, T., Hamada, M., et al.Inhibition of phosphatidylinositol kinase by toyocamycinJ.Antibiot.(Tokyo)43(12)1586-1589(1990) 5.Kiburu, I.N., and LaRonde-LaBlanc, N.Interaction of Rio1 kinase with toyocamycin reveals a conformational switch that controls oligomeric state and catalytic activityPLoS One7(5)(2016)
| Cas No. | N/A | SDF | |
| 别名 | NSC 63701, NSC 99843 | ||
| Canonical SMILES | O[C@H]1[C@H](N2C=C(C#N)C3=C2N=CN=C3N)O[C@H](CO)[C@H]1O | ||
| 分子式 | C12H13N5O4.XH2O | 分子量 | 291.3 |
| 溶解度 | DMF: 50 mg/mL,DMF:PBS(pH 7.2)(1:1): 0.5 mg/mL,DMSO: 30 mg/mL,Ethanol: 0.5 mg/mL | 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 | 3.4329 mL | 17.1644 mL | 34.3289 mL |
| 5 mM | 0.6866 mL | 3.4329 mL | 6.8658 mL |
| 10 mM | 0.3433 mL | 1.7164 mL | 3.4329 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。
The alpha subunit of nitrile hydratase is sufficient for catalytic activity and post-translational modification
Biochemistry 2014 Jun 24;53(24):3990-4.PMID:24914472DOI:10.1021/bi500260j.
Nitrile hydratases (NHases) possess a mononuclear iron or cobalt cofactor whose coordination environment includes rare post-translationally oxidized cysteine sulfenic and sulfinic acid ligands. This cofactor is located in the α-subunit at the interfacial active site of the heterodimeric enzyme. Unlike canonical NHases, Toyocamycin nitrile hydratase (TNHase) from Streptomyces rimosus is a unique three-subunit member of this family involved in the biosynthesis of pyrrolopyrimidine antibiotics. The subunits of TNHase are homologous to the α- and β-subunits of prototypical NHases. Herein we report the expression, purification, and characterization of the α-subunit of TNHase. The UV-visible, EPR, and mass spectra of the α-subunit TNHase provide evidence that this subunit alone is capable of synthesizing the active site complex with full post-translational modifications. Remarkably, the isolated post-translationally modified α-subunit is also catalytically active with the natural substrate, Toyocamycin, as well as the niacin precursor 3-cyanopyridine. Comparisons of the steady state kinetic parameters of the single subunit variant to the heterotrimeric protein clearly show that the additional subunits impart substrate specificity and catalytic efficiency. We conclude that the α-subunit is the minimal sequence needed for nitrile hydration providing a simplified scaffold to study the mechanism and post-translational modification of this important class of catalysts.
Refining the Structural Model of a Heterohexameric Protein Complex: Surface Induced Dissociation and Ion Mobility Provide Key Connectivity and Topology Information
ACS Cent Sci 2015 Dec 23;1(9):477-487.PMID:26744735DOI:10.1021/acscentsci.5b00251.
Toyocamycin nitrile hydratase (TNH) is a protein hexamer that catalyzes the hydration of Toyocamycin to produce sangivamycin. The structure of hexameric TNH and the arrangement of subunits within the complex, however, have not been solved by NMR or X-ray crystallography. Native mass spectrometry (MS) clearly shows that TNH is composed of two copies each of the α, β, and γ subunits. Previous surface induced dissociation (SID) tandem mass spectrometry on a quadrupole time-of-flight (QTOF) platform suggests that the TNH hexamer is a dimer composed of two αβγ trimers; furthermore, the results suggest that α-β interact most strongly (Blackwell et al. Anal. Chem. 2011, 83, 2862-2865). Here, multiple complementary MS based approaches and homology modeling have been applied to refine the structure of TNH. Solution-phase organic solvent disruption coupled with native MS agrees with the previous SID results. By coupling surface induced dissociation with ion mobility mass spectrometry (SID/IM), further information on the intersubunit contacts and relative interfacial strengths are obtained. The results show that TNH is a dimer of αβγ trimers, that within the trimer the α, β subunits bind most strongly, and that the primary contact between the two trimers is through a γ-γ interface. Collisional cross sections (CCSs) measured from IM experiments are used as constraints for postulating the arrangement of the subunits represented by coarse-grained spheres. Covalent labeling (surface mapping) together with protein complex homology modeling and docking of trimers to form hexamer are utilized with all the above information to propose the likely quaternary structure of TNH, with chemical cross-linking providing cross-links consistent with the proposed structure. The novel feature of this approach is the use of SID-MS with ion mobility to define complete connectivity and relative interfacial areas of a heterohexameric protein complex, providing much more information than is available from solution disruption. That information, when combined with CCS-guided coarse-grained modeling and covalent labeling restraints for homology modeling and trimer-trimer docking, provides atomic models of a previously uncharacterized heterohexameric protein complex.