KOdiA-PC
目录号 : GC44011
A potent CD36 ligand
Cas No.:439904-33-3
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
Oxidized low-density lipoprotien (oxLDL) particles contain low molecular weight species which are cytotoxic and pro-atherogenic. Many of these substances were recently isolated and purified from oxLDL, and identified as phosphatidylcholine species containing a fragmented, oxidized short-chain fatty acid remnant at the sn-2 position. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine, or KOdiA-PC, is one of the most potent CD36 ligands among the oxLDL species. KOdiA-PC confers CD36 scavenger receptor binding affinity to LDL at a frequency of only 2 to 3 KOdiA-PC molecules/LDL particle, and may be one of the more important structural determinants of oxLDL.
| Cas No. | 439904-33-3 | SDF | |
| Canonical SMILES | O=P([O-])(OCC[N+](C)(C)C)OC[C@H](OC(CCCC(/C=C/C(O)=O)=O)=O)COC(CCCCCCCCCCCCCCC)=O | ||
| 分子式 | C32H58NO11P | 分子量 | 663.8 |
| 溶解度 | DMF: .5 mg/ml,DMSO: .5 mg/ml,Ethanol: 30 mg/ml,PBS (pH7.2): 5 mg/ml | 储存条件 | Store at -80°C, protect from light |
| 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 | 1.5065 mL | 7.5324 mL | 15.0648 mL |
| 5 mM | 0.3013 mL | 1.5065 mL | 3.013 mL |
| 10 mM | 0.1506 mL | 0.7532 mL | 1.5065 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。
Suppression of Toll-like receptor 4 activation by endogenous oxidized phosphatidylcholine, KOdiA-PC by inhibiting LPS binding to MD2
Inflamm Res 2013 Jun;62(6):571-80.PMID:23474920DOI:10.1007/s00011-013-0609-0.
Objective: Activation of Toll-like receptor 4 (TLR4) triggers immune and inflammatory events by sensing endogenous danger signals as well as invading pathogens and contributes to the development of chronic inflammatory diseases. In this study, we investigated effect of 1-palmitoyl-2-(5-keto-6-octenedioyl)-sn-glycero-3-phosphocholine (KOdiA-PC), an oxidized phosphatidylcholine, on TLR4 activation and the underlying regulatory mechanism. Methods: RAW264.7 macrophages were used for the study. The levels of TNF-α, IFN-β, and COX-2 mRNA and protein were determined by quantitative PCR and ELISA, respectively. Activation of TLR4-signaling was examined by immunoblot and luciferase reporter assays. In vitro binding assay was performed to determine LPS binding to MD2. Macrophage migration was analyzed using a transwell-culture system. Results: KOdiA-PC prevented the activation of TLR4-signaling components including ERK, JNK, p38, NF-κB, and IRF3 leading to decrease of TNF-α, IFN-β, and COX-2 expression. In vitro binding assay revealed that KOdiA-PC interrupted LPS binding to MD2, a TLR4 co-receptor. Consistently, KOdiA-PC suppressed LPS-induced macrophage migration. Conclusion: The results demonstrate that KOdiA-PC can modulate TLR4 activation by regulating ligand-receptor interaction. Therefore, endogenously generated, oxidized phospholipids may play a role in resolving inflammation by terminating TLR activation and macrophage recruitment to the inflamed site.
Anti-atherogenic effects of CD36-targeted epigallocatechin gallate-loaded nanoparticles
J Control Release 2019 Jun 10;303:263-273.PMID:30999008DOI:10.1016/j.jconrel.2019.04.018.
Intimal macrophages play a critical role in atherosclerotic lesion initiation and progression by taking up oxidized low-density lipoprotein (oxLDL) and promoting inflammatory process. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine (KOdiA-PC), a major type of oxidized phosphatidylcholines (PC) found on oxLDL, has a high binding affinity to the macrophage scavenger receptor CD36 and participates in CD36-mediated recognition and uptake of oxLDL by intimal macrophages. We successfully synthesized epigallocatechin gallate (EGCG)-loaded nanoparticles (Enano), which were composed of EGCG, PC, (+) alpha-tocopherol acetate, and surfactant. We also incorporated KOdiA-PC on the surface of Enano to make ligand-coated Enano (L-Enano) to target intimal macrophages. The objectives of this study were to determine the anti-atherogenic effects of Enano and L-Enano in LDL receptor null (LDLr-/-) mice. Our in vitro data demonstrated that L-Enano had a higher binding affinity to mouse peritoneal macrophages than Enano. This high binding affinity was diminished by CD36 antibodies or knockdown of the CD36 receptor in mouse peritoneal macrophages, confirming the specific binding of L-Enano to the macrophage CD36 receptor. LDLr-/- mice were randomly divided to six groups and received weekly tail vein injection with PBS, EGCG, void nanoparticles (Vnano), Enano, ligand-coated Vnano (L-Vnano), or L-Enano once per week for 22 weeks. The dose of EGCG was 25 mg per kg body weight. L-Enano at 20 μg/mL significantly decreased production of monocyte chemoattractant protein-1, tumor necrosis factor alpha, and interleukin-6 from mouse macrophages, while having no effect on their plasma levels compared to the PBS control. There were no significant differences in blood lipid profiles among six treatment groups. Mice treated with L-Enano also had significantly smaller lesion surface areas on aortic arches compared to the PBS control. Liver EGCG content was decreased by treatments in the order of EGCG>Enano>L-Enano. Native EGCG had inhibitory effects on liver and body fat accumulation. This molecular target approach signals an important step towards inhibiting atherosclerosis development via targeted delivery of bioactive compounds to intimal macrophages.
A role of CD36 in the perception of an oxidised phospholipid species in mice
Biomed Res 2015;36(5):303-11.PMID:26522147DOI:10.2220/biomedres.36.303.
CD36 is a broadly expressed transmembrane protein that engages multiple ligands, including polar lipids. This protein is thought to even contribute to the chemosensory detection of long-chain fatty acids in the oral cavity of rodents. In this study, we assessed whether animals consciously perceive a ligand of CD36, 1-(palmitoyl)-2-(5-keto-6-octanedioyl)phosphatidylcholine (KOdiA-PC), and if so, whether CD36 is involved in sensing the oxidised phospholipid species. We found that mice avoided or hesitated to ingest fluids containing KOdiA-PC, suggesting a conscious perception of the lipid in the animals. We assessed the involvement and role of CD36 in the KOdiA-PC perception by comparing the behavioural responses of wild-type and CD36-deficient mice to the test fluids, and provided evidence that the protein could play a role in sensing a lower level of the lipid. We also found that transection of the olfactory nerve of wild-type mice resulted in an inability to perceive KOdiA-PC, suggesting the significance of olfactory system in the lipid sensing. Our findings, coupled with the recent finding of CD36 expression in the mouse olfactory epithelium, led us to predict that the site of CD36 action in the KOdiA-PC sensing plausibly lies within the nasal cavity of the animal.
Rapamycin-Loaded Polymeric Nanoparticles as an Advanced Formulation for Macrophage Targeting in Atherosclerosis
Pharmaceutics 2021 Apr 7;13(4):503.PMID:33916918DOI:10.3390/pharmaceutics13040503.
Recently, rapamycin (Rapa) represents a potential drug treatment to induce regression of atherosclerotic plaques; however, its use requires site-specific accumulation in the vessels involved in the formation of the plaques to avoid the systemic effects resulting from its indiscriminate biodistribution. In this work, a stable pharmaceutical formulation for Rapa was realized as a dried powder to be dispersed extemporaneously before administration. The latter was constituted by mannitol (Man) as an excipient and a Rapa-loaded polymeric nanoparticle carrier. These nanoparticles were obtained by nanoprecipitation and using as a starting polymeric material a polycaprolactone (PCL)/α,β-poly(N-2-hydroxyethyl)-dl-aspartamide (PHEA) graft copolymer. To obtain nanoparticles targeted to macrophages, an oxidized phospholipid with a high affinity for the CD36 receptor of macrophages, the 1-(palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine (KOdiA-PC), was added to the starting organic phase. The chemical-physical and technological characterization of the obtained nanoparticles demonstrated that: both the drug loading (DL%) and the entrapment efficiency (EE%) entrapped drug are high; the entrapped drug is in the amorphous state, protected from degradation and slowly released from the polymeric matrix; and the KOdiA-PC is on the nanoparticle surface (KP-Nano). The biological characterization demonstrated that both systems are quickly internalized by macrophages while maintaining the activity of the drug. In vitro studies demonstrated that the effect of KP-Nano Rapa-loaded, in reducing the amount of the Phospo-Ser757-ULK1 protein through the inhibition of the mammalian target of rapamycin (mTOR), is comparable to that of the free drug.
Assessment of direct interaction between CD36 and an oxidized glycerophospholipid species
J Biochem 2017 Sep 1;162(3):163-172.PMID:28338861DOI:10.1093/jb/mvx019.
Cluster of differentiation 36 (CD36) is a transmembrane protein that recognizes multiple diverse ligands. It is believed that (i) oxidized glycerophosphatidylcholine species having a terminal γ-hydroxyl(or oxo)-α,β-unsaturated carbonyl on the sn-2 acyl group (oxGPCCD36), which can occur on the surface of lipoprotein particles, serve as high-affinity ligands for CD36, and (ii) the amino acid 150-168 of CD36 (CD36150-168) is responsible for recognizing oxGPCCD36. However, it remains uncertain whether CD36150-168 directly interacts with oxGPCCD36 alone. In this study, we addressed this issue by investigating and comparing the banding pattern by non-denaturing polyacrylamide gel electrophoresis of a glutathione S-transferase (GST) fusion protein containing CD36150-168 (GST-CD36150-168), in the presence and absence of an oxGPCCD36 species, 1-(palmitoyl)-2-(5-keto-6-octenedioyl)phosphatidylcholine (KOdiA-PC). It was shown that GST-CD36150-168 pre-incubated with KOdiA-PC produced bands at upper positions than did the fusion protein alone. Further analyses revealed that the bands produced by the loading of GST-CD36150-168/KOdiA-PC mixture represent complexes consisting of the fusion protein and lipid. To our knowledge, this is the first evidence for direct interaction between CD36150-168 and oxGPCCD36 alone. It is also notable that the electrophoresis-based technique provides a convenient means to evaluate protein-lipid interactions.