LLP-3
目录号 : GC44080
Induces apoptosis by blocking Survivin/Ran interactions
Cas No.:1453835-43-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Survivin (also known as baculoviral IAP repeat-containing protein 5 (BIRC5)) is a member of the inhibitor of apoptosis (IAP) family that interacts with and inhibits the apoptotic function of several proteins. LLP-3 is a cell-permeable ligand of Survivin that blocks its interaction with Ran, resulting in the induction of apoptosis (IAP) in glioma stem cells (IC50 = 31 µM). It abolishes the growth of glioblastoma multiforme cell in spheres and in tumor slice cultures.
| Cas No. | 1453835-43-2 | SDF | |
| Canonical SMILES | O=C1NC(C2=C(O)C=CC(Cl)=C2)=CC(C3=CC(OCC4=CC=CC=C4)=CC(OCC5=CC=CC=C5)=C3)=C1C#N | ||
| 分子式 | C32H23ClN2O4 | 分子量 | 535 |
| 溶解度 | DMF: 2 mg/ml,DMF:PBS(pH7.2) (1:2): 0.3 mg/ml,DMSO: 2 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 | 1.8692 mL | 9.3458 mL | 18.6916 mL |
| 5 mM | 0.3738 mL | 1.8692 mL | 3.7383 mL |
| 10 mM | 0.1869 mL | 0.9346 mL | 1.8692 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。
Characterization and antioxidant activities of polysaccharides from the leaves of Lilium lancifolium Thunb
Int J Biol Macromol 2016 Nov;92:148-155.PMID:27397720DOI:10.1016/j.ijbiomac.2016.07.028.
In this study, LLP-1, LLP-2, and LLP-3 three novel polysaccharide fractions were purified from the leaves of Lilium lancifolium, and their physicochemical characterizations and antioxidant properties were investigated by chemical methods, high performance gel permeation chromatography (HPGPC), high performance liquid chromatography (HPLC), fourier transform infrared spectrometry (FT-IR), scanning electron microscopy (SEM), and DPPH radical assay, hydroxyl radical assay, superoxide radical assay and ferrous ion chelating assay, respectively. Results showed that LLP-1, LLP-2, and LLP-3 had low protein and uronic acid contents, meanwhile, their weight-average molecular weight were estimated to be 2.25×106, 2.02×106, and 2.08×106Da, respectively. Mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose glucose and galactose were the major monosaccaherides components presenting in the polysaccharide fractions. Three polysaccharide fractions were not observed triple-helical conformation, while possessed variant surface structure. In addition, three polysaccharide fractions all exhibited significantly scavenging activities against free radical and chelate Fe2+in vitro.
Isolation, purification, structural analysis and coagulatory activity of water-soluble polysaccharides from Ligustrum lucidum Ait flowers
Chem Cent J 2017 Oct 4;11(1):98.PMID:29086873DOI:10.1186/s13065-017-0332-y.
In this study, Ligustrum lucidum flowers as raw material, the extraction, isolation and coagulatory activity of polysaccharides were carried out for the first time. The crude polysaccharide was obtained by hot water extraction and ethanol precipitation, and preliminarily purified by Sevage method and D101 macroporous resin. Then the polysaccharide was further purified by DEAE-52 cellulose and Sephadex G-100 column chromatography, respectively. The structural characteristics were detected by LC, GC, FT-IR and NMR. Furthermore, the coagulatory activity of the polysaccharides were investigated by APTT, TT, PT and FIB assays in vitro. The results demonstrated that four polysaccharides were isolated from flowers of L. lucidum, named as LLP-1a, LLP-1b, LLP-2 and LLP-3, and the yields were 0.039, 0.0054, 0.0055 and 0.017%, respectively based on the weight of the dried flowers. The four polysaccharides components were free of nucleic acids and proteins, and their average molecular weights were 25,912, 64,919, 3,940,246 and 2,975,091 g/mol, respectively. The monosaccharide compositions of LLp-1a were L-rhamnose, L-arabinose, D-xylose, D-glucose and D-galactose (molar ratio of 3.16: 2.46: 1.00: 7.27: 4.22). Only D-galactose was detected from LLp-1b. LLp-2 was composed of L-arabinose, D-glucose and D-galactose (molar ratio of 1.28:1.32:1.00). LLP-3 was composed of L-rhamnose, L-arabinose, D-xylose, D-glucose and D-galactose (molar ratio of 5.85: 2.21: 2.23: 1.00: 2.25). Coagulation assays indicated that LLp-1a and LLP-3 had good anticoagulant effect in vitro, while LLp-1b showed procoagulant activity.
The cytoplasmic domain of human immunodeficiency virus type 1 transmembrane protein gp41 harbors lipid raft association determinants
J Virol 2010 Jan;84(1):59-75.PMID:19793805DOI:10.1128/JVI.00899-09.
The molecular basis for localization of the human immunodeficiency virus type 1 envelope glycoprotein (Env) in detergent-resistant membranes (DRMs), also called lipid rafts, still remains unclear. The C-terminal cytoplasmic tail of gp41 contains three membrane-interacting, amphipathic alpha-helical sequences, termed lentivirus lytic peptide 2 (LLP-2), LLP-3, and LLP-1, in that order. Here we identify determinants in the cytoplasmic tail which are crucial for Env's association with Triton X-100-resistant rafts. Truncations of LLP-1 greatly reduced Env localization in lipid rafts, and the property of Gag-independent gp41 localization in rafts was conserved among different strains. Analyses of mutants containing single deletions or substitutions in LLP-1 showed that the alpha-helical structure of the LLP-1 hydrophobic face has a more-critical role in Env-raft associations than that of the hydrophilic face. With the exception of a Pro substitution for Val-833, all Pro substitution and charge-inverting mutants showed wild-type virus-like one-cycle viral infectivity, replication kinetics, and Env incorporation into the virus. The intracellular localization and cell surface expression of mutants not localized in lipid rafts, such as the TM844, TM813, 829P, and 843P mutants, were apparently normal compared to those of wild-type Env. Cytoplasmic subdomain targeting analyses revealed that the sequence spanning LLP-3 and LLP-1 could target a cytoplasmic reporter protein to DRMs. Mutations of LLP-1 that affected Env association with lipid rafts also disrupted the DRM-targeting ability of the LLP-3/LLP-1 sequence. Our results clearly demonstrate that LLP motifs located in the C-terminal cytoplasmic tail of gp41 harbor Triton X-100-resistant raft association determinants.
Impairment of glioma stem cell survival and growth by a novel inhibitor for Survivin-Ran protein complex
Clin Cancer Res 2013 Feb 1;19(3):631-42.PMID:23251006DOI:10.1158/1078-0432.CCR-12-0647.
Purpose: Glioblastoma multiforme (GBM) is a devastating disease. Recent studies suggest that the stem cell properties of GBM contribute to the development of therapy resistance. Experimental design: The expression of Survivin and Ran was evaluated by immunohistochemistry with GBM tissues, and quantitative reverse transcriptase (qRT)-PCR and immunocytochemistry with patient-derived GBM sphere cultures. With a computational structure-based drug design, 11 small-molecule compounds were designed, synthesized, and evaluated as inhibitor candidates for the molecular interaction of Survivin protein. The molecular mechanism of the lead compound, LLP-3, was determined by Western blot, ELISA, in situ proximity ligation assay, and immunocytochemistry. The effects of LLP-3 treatment on GSCs were evaluated both in vitro and in vivo. Quantitative immunohistochemistry was carried out to compare Survivin expression in tissues from 44 newly diagnosed and 31 recurrent post-chemoradiation GBM patients. Lastly, the sensitivities of temozolomide-resistant GBM spheres to LLP-3 were evaluated in vitro. Results: Survivin and Ran were strongly expressed in GBM tissues, particularly in the perivasculature, and also in patient-derived GSC cultures. LLP-3 treatment disrupted the Survivin-Ran protein complex in cancer cells and abolished the growth of patient-derived GBM spheres in vitro and in vivo. This inhibition was dependent on caspase activity and associated with p53 status of cells. Immunohistochemistry showed that Survivin expression is significantly increased in recurrent GBM compared with newly diagnosed tumors, and temozolomide-resistant GBM spheres exhibited high sensitivities to LLP-3 treatment. Conclusions: Disruption of the Survivin-Ran complex by LLP-3 abolishes survival and growth of GSCs both in vitro and in vivo, indicating an attractive novel therapeutic approach for GBM.
HIV-1 Cell-Free and Cell-to-Cell Infections Are Differentially Regulated by Distinct Determinants in the Env gp41 Cytoplasmic Tail
J Virol 2015 Sep;89(18):9324-37.PMID:26136566DOI:10.1128/JVI.00655-15.
The HIV-1 envelope (Env) glycoprotein mediates viral entry during both cell-free and cell-to-cell infection of CD4(+) T cells. The highly conserved long cytoplasmic tail (CT) of Env is required in a cell type-dependent manner for optimal infectivity of cell-free virus. To probe the role of the CT in cell-to-cell infection, we tested a panel of mutations in the CT region that maintain or attenuate cell-free infection to investigate whether the functions of the CT are conserved during cell-free and cell-to-cell infection. The mutations tested included truncations of structural motifs in the gp41 CT and two point mutations in lentiviral lytic peptide 3 (LLP-3) previously described as disrupting the infectivity of cell-free virus. We found that small truncations of 28 to 43 amino acids (aa) or two LLP-3 point mutations, YW_SL and LL_RQ, severely impaired single-round cell-free infectivity 10-fold or more relative to wild-type full-length CT. These mutants showed a modest 2-fold reduction in cell-to-cell infection assays. Conversely, large truncations of 93 to 124 aa severely impaired cell-to-cell infectivity 20-fold or more while resulting in a 50% increase in infectivity of cell-free viral particles when produced in 293T cells. Intermediate truncations of 46 to 90 aa showed profound impairment of both modes of infection. Our results show that the abilities of Env to support cell-free and cell-to-cell infection are genetically distinct. These differences are cell type dependent for large-CT-truncation mutants. Additionally, point mutants in LLP-3 can maintain multiround propagation from cell-to-cell in primary CD4(+) T cells. Importance: The functions of HIV Env gp41 CT remain poorly understood despite being widely studied in the context of cell-free infection. We have identified domains of the gp41 CT responsible for striking selective deficiencies in either cell-free or cell-to-cell infectivity. These differences may reflect a different intrinsic regulatory influence of the CT on cell-associated versus particle-associated Env or differential interaction with host or viral proteins. Our findings provide novel insight into the key regulatory potential of the gp41 CT in cell-free and cell-to-cell HIV-1 infection, particularly for short-truncation mutants of ≤43 amino acids or mutants with point mutations in the LLP-3 helical domain of the CT, which are able to propagate via cell-to-cell infection in the absence of infectious cell-free virus production. These mutants may also serve as tools to further define the contributions of cell-free and cell-to-cell infection in vitro and in vivo.