TBPB
目录号 : GC37749
An allosteric agonist of M1 receptors
Cas No.:634616-95-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
TBPB is an allosteric agonist of M1 muscarinic acetylcholine receptors (mAChRs; EC50 = 158 nM in CHO-K1 cells expressing rat recombinant receptors).1 It is selective for M1 over M2-5 receptors at concentrations up to 10 μM. TBPB (3 μM) potentiates NMDA-evoked currents in CA1 pyramidal cells. It increases production of the non-amyloidogenic amyloid precursor protein (APP) cleavage products APPsα and CTFα in PC12 cells overexpressing the human M1 receptor and APP when used at a concentration of 1 μM. TBPB decreases amphetamine-induced hyperlocomotion in a rat model that is predictive of antipsychotic-like activity.
1.Jones, C.K., Brady, A.E., Davis, A.A., et al.Novel selective allosteric activator of the M1 muscarinic acetylcholine receptor regulates amyloid processing and produces antipsychotic-like activity in ratsJ. Neurosci.28(41)10422-10433(2008)
| Cas No. | 634616-95-8 | SDF | |
| Canonical SMILES | O=C1N(C2CCN(C3CCN(CC4=C(C)C=CC=C4)CC3)CC2)C5=CC=CC=C5N1 | ||
| 分子式 | C25H32N4O | 分子量 | 404.55 |
| 溶解度 | DMSO: 22.5 mg/mL (55.62 mM and warming) | 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 | 2.4719 mL | 12.3594 mL | 24.7188 mL |
| 5 mM | 0.4944 mL | 2.4719 mL | 4.9438 mL |
| 10 mM | 0.2472 mL | 1.2359 mL | 2.4719 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。
TBPEH-TBPB Initiate the Radical Addition of Benzaldehyde and Allyl Esters
Int J Mol Sci 2022 Nov 8;23(22):13704.PMID:36430186DOI:10.3390/ijms232213704.
Tert-butylperoxy-2-ethylhexanoate (TBPEH) and tert-butyl peroxybenzoate (TBPB) promote the radical acylation of allyl ester with benzaldehyde to synthesize new carbonyl-containing compounds under solvent-free and metal-free conditions. This reaction is compatible with electron-donating and halogen groups and has excellent atom utilization and chemical selectivity. Furthermore, the synthetic compounds can further apply to the preparation of lactone, piperidine, tetrazole and oxazole.
Conserved regions of gonococcal TBPB are critical for surface exposure and transferrin iron utilization
Infect Immun 2013 Sep;81(9):3442-50.PMID:23836816DOI:10.1128/IAI.00280-13.
The transferrin-binding proteins TbpA and TBPB enable Neisseria gonorrhoeae to obtain iron from human transferrin. The lipoprotein TBPB facilitates, but is not strictly required for, TbpA-mediated iron acquisition. The goal of the current study was to determine the contribution of two conserved regions within TBPB to the function of this protein. Using site-directed mutagenesis, the first mutation we constructed replaced the lipobox (LSAC) of TBPB with a signal I peptidase cleavage site (LAAA), while the second mutation deleted a conserved stretch of glycine residues immediately downstream of the lipobox. We then evaluated the resulting mutants for effects on TBPB expression, surface exposure, and transferrin iron utilization. Western blot analysis and palmitate labeling indicated that the lipobox, but not the glycine-rich motif, is required for lipidation of TBPB and tethering to the outer membrane. TBPB was released into the supernatant by the mutant that produces TBPB LSAC. Neither mutation disrupted the transport of TBPB across the bacterial cell envelope. When these mutant TBPB proteins were produced in a strain expressing a form of TbpA that requires TBPB for iron acquisition, growth on transferrin was either abrogated or dramatically diminished. We conclude that surface tethering of TBPB is required for optimal performance of the transferrin iron acquisition system, while the presence of the polyglycine stretch near the amino terminus of TBPB contributes significantly to transferrin iron transport function. Overall, these results provide important insights into the functional roles of two conserved motifs of TBPB, enhancing our understanding of this critical iron uptake system.
TbpBY167A-Based Vaccine Can Protect Pigs against Glässer's Disease Triggered by Glaesserella parasuis SV7 Expressing TBPB Cluster I
Pathogens 2022 Jul 4;11(7):766.PMID:35890011DOI:10.3390/pathogens11070766.
Glaesserella parasuis is the etiological agent of Glässer's disease (GD), one of the most important diseases afflicting pigs in the nursery phase. We analyzed the genetic and immunological properties of the TBPB protein naturally expressed by 27 different clinical isolates of G. parasuis that were typed as serovar 7 and isolated from pigs suffering from GD. All the strains were classified as virulent by LS-PCR. The phylogenetic analyses demonstrated high similarity within the amino acid sequence of TBPB from 24 clinical strains all belonging to cluster III of TBPB, as does the protective antigen TbpBY167A. Three G. parasuis isolates expressed cluster I TbpBs, indicating antigenic diversity within the SV7 group of G. parasuis. The antigenic analysis demonstrated the presence of common epitopes on all variants of the TBPB protein, which could be recognized by an in vitro analysis using pig IgG induced by a TbpBY167A-based vaccine. The proof of concept of the complete cross-protection between clusters I and III was performed in SPF pigs immunized with the TbpBY167A-based vaccine (cluster III) and challenged with G. parasuis SV7, strains LM 360.18 (cluster I). Additionally, pigs immunized with a whole-cell inactivated vaccine based on G. parasuis SV5 (Nagasaki strain) did not survive the challenge performed with SV7 (strain 360.18), demonstrating the absence of cross-protection between these two serovars. Based on these results, we propose that a properly formulated TbpBY167A-based vaccine may elicit a protective antibody response against all strains of G. parasuis SV7, despite TBPB antigenic diversity, and this might be extrapolated to other serovars. This result highlights the promising use of the TbpBY167A antigen in a future commercial vaccine for GD prevention.
Identification of transferrin-binding domains in TBPB expressed by Neisseria gonorrhoeae
Infect Immun 2007 Jul;75(7):3220-32.PMID:17438025DOI:10.1128/IAI.00072-07.
The transferrin iron acquisition system of Neisseria gonorrhoeae is necessary for iron uptake from transferrin in the human host and requires the participation of two distinct proteins: TbpA and TBPB. TbpA is a TonB-dependent outer membrane transporter responsible for the transport of iron into the cell. TBPB is a lipid-modified protein, for which a precise role in receptor function has not yet been elucidated. These receptor complex proteins show promise as vaccine candidates; therefore, it is important to identify surface-exposed regions of the proteins required for wild-type functions. In this study we examined TBPB, which has been reported to be surface exposed in its entirety; however, this hypothesis has never been tested experimentally. We placed the hemagglutinin (HA) epitope into TBPB with the dual purpose of examining the surface exposure of particular epitopes as well as their impact on receptor function. Nine insertion mutants were created, placing the epitope downstream of the signal peptidase II cleavage site. We report that the HA epitope is surface accessible in all mutants, indicating that the full-length TBPB is completely surface exposed. By expressing the TbpB-HA fusion proteins in N. gonorrhoeae, we were able to examine the impact of each insertion on the function of TBPB and the transferrin acquisition process. We propose that TBPB is comprised of two transferrin-binding-competent lobes, both of which are critical for efficient iron uptake from human transferrin.
Vaccination of mice with gonococcal TBPB expressed in vivo from Venezuelan equine encephalitis viral replicon particles
Infect Immun 2006 Mar;74(3):1612-20.PMID:16495532DOI:10.1128/IAI.74.3.1612-1620.2006.
We investigated the immunogenicity of gonococcal transferrin binding protein B (TBPB) expressed with and without a eukaryotic secretion signal from a nonpropagating Venezuelan equine encephalitis virus replicon particle (VRP) delivery system. TBPB was successfully expressed in baby hamster kidney (BHK) cells, and the presence of the eukaryotic secretion signal not only apparently increased the protein's expression but also allowed for extracellular localization and glycosylation. Mice immunized with VRPs produced significant amounts of serum antibody although less than the amounts produced by mice immunized with recombinant protein. The response of mice immunized with VRPs encoding TBPB was consistently more Th1 biased than the response of mice immunized with recombinant protein alone. Boosting with recombinant protein following immunization with TBPB VRPs resulted in higher specific-antibody levels without altering the Th1/Th2 bias. Most of the immunization groups produced significant specific antibody binding to the intact surface of the homologous Neisseria gonorrhoeae strain. Immunization with TBPB VRPs without a eukaryotic secretion signal generated no measurable specific antibodies on the genital mucosal surface, but inclusion of a eukaryotic secretion signal or boosting with recombinant protein resulted in specific immunoglobulin G (IgG) and IgA in mucosal secretions after TBPB VRP immunization. The TBPB VRP system has potential for an N. gonorrhoeae vaccine.