DC-Chol (hydrochloride)
(Synonyms: O-[(N,N-二甲基氨基乙基)-氨基甲酰基]胆固醇盐酸盐,?Cholesteryl 3β-N-(dimethylaminoethyl)carbamate) 目录号 : GC43385
A cationic cholesterol
Cas No.:166023-21-8
Sample solution is provided at 25 µL, 10mM.
Quality Control & SDS
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- Purity: >97.00%
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- SDS (Safety Data Sheet)
- Datasheet
| Atomic Force Microscopy (AFM) [1]: | |
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Substrate |
Aβ40 |
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Preparation Method |
Aβ40 (30 μM) in pH 7.4 phosphate buffer incubated on a Speci-Mix aliquot mixer. Aβ40 in the presence of 50 ng/mL cholesterol-SO4, 500 μg/mL cholesterol-SO4, 50 ng/mL DC-Chol (hydrochloride), and 500 μg/mL DC-cholesterol |
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Reaction Conditions |
50/500 ng/mL DC-Chol (hydrochloride) with Aβ40 for 17h |
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Applications |
For DC-Chol (hydrochloride), Aβ fibers were observed in the image of Aβ40 (30 μM) coincubated with low concentration of DC-cholesterol (50 ng/mL). However, in the presence of 500 μg/mL DC-cholesterol, no fiber structures were found in the image. |
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References: [1]. Elbassal EA, Liu H, et,al. Effects of Charged Cholesterol Derivatives on Aβ40 Amyloid Formation. J Phys Chem B. 2016 Jan 14;120(1):59-68. doi: 10.1021/acs.jpcb.5b09557. Epub 2015 Dec 23. PMID: 26652010; PMCID: PMC4959543. |
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DC-Chol(hydrochloric acid) can inhibit the formation of Aβ40 fibers,DC-Chol(hydrochloric acid) can inhibit the amyloid formation of oxidized hCT[1,2].
For DC-Chol (hydrochloride), Aβ fibers were observed in the image of Aβ40 (30 µM) coincubated with low concentration of DC-Chol (hydrochloride) (50 ng/mL). However, in the presence of 500 µg/mL DC-Chol (hydrochloride), no fiber structures were found in the image[1]. DC-Chol/DOPE cationic liposomes properly condense and compact CT-DNA by means of a strong entropically driven surface electrostatic interaction[3]. Lipoplexes constituted by calf-thymus DNA (CT-DNA) and mixed cationic liposomes consisting of varying proportions of the cationic lipid 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol hydrochloride (DC-Chol (hydrochloride)) and DOPE have been analyzed. DC-Chol/DOPE liposomes, with a mean hydrodynamic diameter of around (120±10) nm, compact and condense DNA fragments at their cationic surfaces by means of a strong entropically driven electrostatic interaction[4]. Formulations prepared with 50 mol% DODAC or DC-Chol (hydrochloride), and 20 mol% DSPE-PEG(2000) exhibited circulation half-lives ranging from 6.5 to 12.5 h. DC-Chol (hydrochloride) formulations prepared with DSPE-PEG(2000) accumulated threefold higher in s.c. HT29 tumors than its PEG-free counterpart[6]. DC-Chol (hydrochloride) is internalized through macrocytosis and clathrin-mediated endocytosis [5].
References:
[1]. Elbassal EA, Liu H, et,al. Effects of Charged Cholesterol Derivatives on Aβ40 Amyloid Formation. J Phys Chem B. 2016 Jan 14;120(1):59-68. doi: 10.1021/acs.jpcb.5b09557. Epub 2015 Dec 23. PMID: 26652010; PMCID: PMC4959543.
[2]. Lantz R, Busbee B, et,al. Effects of disulfide bond and cholesterol derivatives on human calcitonin amyloid formation. Biopolymers. 2020 May;111(5):e23343. doi: 10.1002/bip.23343. Epub 2019 Dec 5. PMID: 31804717; PMCID: PMC9254112.
[3]. RodrÍguez-Pulido A, Ortega F, et,al. A physicochemical characterization of the interaction between DC-Chol/DOPE cationic liposomes and DNA. J Phys Chem B. 2008 Oct 2;112(39):12555-65. doi: 10.1021/jp804066t. Epub 2008 Aug 27. PMID: 18729499.
[4]. MuÑoz-Ubeda M, RodrÍguez-Pulido A, et,al. Effect of lipid composition on the structure and theoretical phase diagrams of DC-Chol/DOPE-DNA lipoplexes. Biomacromolecules. 2010 Dec 13;11(12):3332-40. doi: 10.1021/bm1008124. Epub 2010 Nov 8. PMID: 21058732.
[5]. Rapaka H, Manturthi S, et,al. Effect of Methylation of the Hydrophilic Domain of Tocopheryl Ammonium-Based Lipids on their Nucleic Acid Delivery Properties. ACS Omega. 2022 Apr 29;7(18):15396-15403. doi: 10.1021/acsomega.1c06889. PMID: 35571792; PMCID: PMC9096827.
[6]. Ho EA, Ramsay E, et,al. Characterization of cationic liposome formulations designed to exhibit extended plasma residence times and tumor vasculature targeting properties. J Pharm Sci. 2010 Jun;99(6):2839-53. doi: 10.1002/jps.22043. PMID: 20091826.
DC-Chol(hydrochlor acid) can inhibit the formation of Aβ40 fibers,DC-Chol(hydrochlor acid) can inhibit the amyloid formation of oxidized hCT[1,2].
对于DC -Chol（盐酸盐），Aβ；在 Aβ40 (30 µM) 与低浓度 DC-Chol（盐酸盐）(50 ng/mL) 共孵育的图像中观察到纤维。然而，在 500 µg/mL DC-Chol（盐酸盐）的存在下，图像中没有发现纤维结构[1]。 DC-Chol/DOPE 阳离子脂质体通过强熵驱动的表面静电相互作用适当地浓缩和压缩 CT-DNA[3]。由小牛胸腺 DNA (CT-DNA) 和由不同比例的阳离子脂质组成的混合阳离子脂质体构成的脂质复合物 3β-[N-(N77777#39;,N77777#39;-二甲基氨基乙烷)-氨甲酰]胆固醇盐酸盐 (DC-Chol (hydrochloride) )) 和 DOPE 已经过分析。 DC-Chol/DOPE 脂质体的平均流体动力学直径约为 (120±10) nm，通过强熵驱动的静电相互作用在其阳离子表面压缩和浓缩 DNA 片段[4]。用 50 mol% DODAC 或 DC-Chol（盐酸盐）和 20 mol% DSPE-PEG(2000) 制备的制剂表现出 6.5 至 12.5 小时的循环半衰期。用 DSPE-PEG(2000) 制备的 DC-Chol（盐酸盐）制剂在 sc 中的积累高出三倍。 HT29 肿瘤优于其不含 PEG 的肿瘤[6]。 DC-Chol（盐酸盐）通过巨细胞作用和网格蛋白介导的内吞作用内化 [5]。
| Cas No. | 166023-21-8 | SDF | |
| 别名 | O-[(N,N-二甲基氨基乙基)-氨基甲酰基]胆固醇盐酸盐,?Cholesteryl 3β-N-(dimethylaminoethyl)carbamate | ||
| 化学名 | (3β)-cholest-5-en-3-ol 3-[N-[2-(dimethylamino)ethyl]carbamate], monohydrochloride | ||
| Canonical SMILES | CC(C)CCC[C@@H](C)[C@@]1([H])CC[C@@]2([H])[C@]3([H])CC=C4C[C@@H](OC(NCCN(C)C)=O)CC[C@]4(C)[C@@]3([H])CC[C@@]21C.Cl | ||
| 分子式 | C32H56N2O2•HCl | 分子量 | 537.3 |
| 溶解度 | 10mg/mL in methanol, 5mg/mL in DMSO | 储存条件 | Store at -20°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 | 1.8612 mL | 9.3058 mL | 18.6116 mL |
| 5 mM | 0.3722 mL | 1.8612 mL | 3.7223 mL |
| 10 mM | 0.1861 mL | 0.9306 mL | 1.8612 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。
A physicochemical characterization of the interaction between DC-Chol/DOPE cationic liposomes and DNA
J Phys Chem B 2008 Oct 2;112(39):12555-65.PMID:18729499DOI:10.1021/jp804066t.
A 1:1 mixture of the cationic lipid 3beta-[ N-( N', N'-dimethylaminoethane)-carbamoyl]cholesterol hydrochloride (DC-Chol) and the zwitterionic lipid, 1,2-dioleoyl- sn-glycero-3-phosphoetanolamine (DOPE), has been used to compact calf-thymus DNA (CT-DNA) in aqueous buffered solution at 298.15 K. The formation process of this lipoplex has been analyzed by means of electrophoretic mobility, cryo-TEM, dynamic light scattering, and fluorescence spectroscopy techniques. The experimental results indicate that DC-Chol/DOPE liposomes are mostly spherical and unilamellar, with a mean diameter of around 99 +/- 10 nm and a bilayer with a thickness of 4.5 +/- 0.5 nm. In the presence of CT-DNA, DC-Chol/DOPE/CT-DNA lipoplexes are formed by means of a strong entropically driven surface electrostatic interaction, as confirmed by zeta potential and fluorescence results, as a consequence of which DNA is compacted and condensed at the surface of the cationic liposomes. The negative charges of DNA phosphate groups are neutralized by the positive charges of cationic liposomes at the isoneutrality L/ D ratio, ( L/ D) varphi around 4, obtained from electrophoretic, fluorescence, and DLS measurements. The decrease in the fluorescence emission intensity of ethidium bromide, EtBr, initially intercalated between DNA base pairs, as long as the association between the biopolymer and the cationic liposomes takes place has permitted one to confirm its electrostatic character as well as to evaluate the different microenvironments of varying polarity of DNA-double helix, liposomes, and/or lipoplexes. Electronic microscopy reveals a rich scenario of possible nanostructures and morphologies for the lipoplexes, from unilamellar DNA-coated liposomes to multilamellar lipoplexes passing through cluster-like structures and several intermediate morphologies.
Effect of lipid composition on the structure and theoretical phase diagrams of DC-Chol/DOPE-DNA lipoplexes
Biomacromolecules 2010 Dec 13;11(12):3332-40.PMID:21058732DOI:10.1021/bm1008124.
Lipoplexes constituted by calf-thymus DNA (CT-DNA) and mixed cationic liposomes consisting of varying proportions of the cationic lipid 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol hydrochloride (DC-Chol) and the zwitterionic lipid, 1,2-dioleoyl-sn-glycero-3-phosphoetanolamine (DOPE) have been analyzed by means of electrophoretic mobility, SAXS, and fluorescence anisotropy experiments, as well as by theoretically calculated phase diagrams. Both experimental and theoretical studies have been run at several liposome and lipoplex compositions, defined in terms of cationic lipid molar fraction, α, and either the mass or charge ratios of the lipoplex, respectively. The experimental electrochemical results indicate that DC-Chol/DOPE liposomes, with a mean hydrodynamic diameter of around (120 ± 10) nm, compact and condense DNA fragments at their cationic surfaces by means of a strong entropically driven electrostatic interaction. Furthermore, the positive charges of cationic liposomes are compensated by the negative charges of DNA phosphate groups at the isoneutrality L/D ratio, (L/D)(ϕ), which decreases with the cationic lipid content of the mixed liposome, for a given DNA concentration. This inversion of sign process has been also studied by means of the phase diagrams calculated with the theoretical model, which confirms all the experimental results. SAXS diffractograms, run at several lipoplex compositions, reveal that, irrespectively of the lipoplex charge ratio, DC-Chol/DOPE-DNA lipoplexes show a lamellar structure, L(α), when the cationic lipid content on the mixed liposomes α ≥ 0.4, while for a lower content (α = 0.2) the lipoplexes show an inverted hexagonal structure, H(II), usually related with improved cell transfection efficiency. A similar conclusion is reached from fluorescence anisotropy results, which indicate that the fluidity on liposome and lipoplexes membrane, also related with better transfection results, increases as long as the cationic lipid content decreases.
Effect of Methylation of the Hydrophilic Domain of Tocopheryl Ammonium-Based Lipids on their Nucleic Acid Delivery Properties
ACS Omega 2022 Apr 29;7(18):15396-15403.PMID:35571792DOI:10.1021/acsomega.1c06889.
Lipid-enabled nucleic acid delivery has garnered tremendous attention in recent times. Tocopherol among the cationic lipids, 3b-[N-(N',N'-dimethylamino-ethane)carbamoyl]-cholesterol hydrochloride (DC-Chol) with a headgroup of dimethylammonium, and cholesterol as a hydrophobic moiety are found to be some of the most successful lipids and are being used in clinical trials. However, limited efficacy is a major limitation for their broader therapeutic application. In our prior studies, we demonstrated tocopherol to be a potential alternative hydrophobic moiety having additional antioxidant properties to develop efficient and safer liposomal formulations. Inspired by DC-Chol applications and taking cues from our own prior findings, herein, we report the design and synthesis of four alpha-tocopherol-based cationic derivatives with varying degrees of methylation, AC-Toc (no methylation), MC-Toc (monomethylation derivative), DC-Toc (dimethylation derivative), and TC-Toc (trimethylation derivative) and the evaluation of their gene delivery properties. The transfection studies showed that AC-Toc liposomes exhibited superior transfection compared to MC-Toc, DC-Toc, TC-Toc, and control DC-Chol, indicating that methylation in the hydrophilic moiety of Toc-lipids reduced their transfection properties. Cellular internalization studies in the presence of different endocytosis blockers revealed that all four tocopherol lipids were internalized through clathrin-mediated endocytosis, whereas control DC-Chol was found to be internalized through both macropinocytosis and clathrin-mediated endocytosis. These novel Toc-lipids exhibited higher antioxidant properties than DC-Chol by generating less reactive oxygen species, indicating lower cytotoxicity. Our present findings suggest that AC-Toc may be considered as an alternative to DC-Chol in liposomal transfections.
The Impact of Lipid Types and Liposomal Formulations on Osteoblast Adiposity and Mineralization
Molecules 2018 Jan 2;23(1):95.PMID:29301300DOI:10.3390/molecules23010095.
Recent studies have demonstrated that fat accumulation in bone cells is detrimental to bone mass. Both adipocytes and osteoblasts are derived from common multipotent mesenchymal stem cells (MSCs) and hence the presence of fat may increase adipocyte proliferation, differentiation and fat accumulation while inhibiting osteoblast differentiation and bone formation. Lipids are common constituents in supramolecular vesicles (e.g., micelles or liposomes) that serve as drug delivery systems. Liposomal formulations such as Meriva® were proven to decrease joint pain and improve joint function in osteoarthritis (OA) patients. In this study, we evaluated how lipid types and liposomal formulations affect osteoblast behavior including cell viability, differentiation, mineralization and inflammation. Various liposomal formulations were prepared using different types of lipids, including phosphatidylcholine (PC), 1,2-dioleoyl-sn-glycero-3-phospho-ethanolamine (DOPE), cholesterol (Chol), 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol hydrochloride (DC-cholesterol HCl), and 1,2-dioleoyl-3-trimethylammonium-propane chloride salt (DOTAP) to investigate the impact on osteoblast differentiation and inflammation. The results indicated that cationic lipids, DC-cholesterol and DOTAP, presented higher dose-dependent cytotoxicity and caused high level of inflammatory responses. Due to the natural properties of lipids, all the lipids can induce lipid droplet formation in osteoblasts but the level of lipid droplet accumulation was different. In comparison with cationic lipids, neutral lipids induced less adiposity, and maintained high osteoblast mineralization. Similar to previous researches, we also confirmed an inverse relationship between lipid droplet formation and osteoblast mineralization in 7F2 mouse osteoblasts. Importantly, PC containing liposomes (PC only and PC/DOTAP) suppressed IL-1β-induced gene expression of COX-2 and MMP-3 but not Chol/DOTAP liposomes or DC-Chol/DOPE liposomes. Taken together, we suggested that PC contained liposomes could provide the best liposomal formulation for the treatment of bone diseases.
Safe and effective delivery of small interfering RNA with polymer- and liposomes-based complexes
Biol Pharm Bull 2013;36(6):995-1001.PMID:23727920DOI:10.1248/bpb.b13-00054.
We developed binary and ternary complexes based on polymers and liposomes for safe and effective delivery of small interfering RNA (siRNA). Anti-luciferase siRNA was used as a model of nucleic acid medicine. The binary complexes of siRNA were prepared with cationic polymers and cationic liposomes such as polyethylenimine (PEI), polyamidoamine (PAMAM) dendrimer, poly-L-arginine (PLA), trimethyl[2,3-(dioleoxy)-propyl]ammonium chloride (DOTMA), and cholesteryl 3β-N-(dimetylaminnoethyl)carbamate hydrochloride (DC-Chol). The ternary complexes were constructed by the addition of γ-polyglutamic acid (γ-PGA) to the binary complexes. The complexes were approximately 54-153 nm in particle size. The binary complexes showed a cationic surface charge although an anionic surface charge was observed in the ternary complexes. The polymer-based complexes did not show a silencing effect in the mouse colon carcinoma cell line expressing luciferase regularly (Colon26/Luc cells). The binary complexes based on liposomes and their ternary complexes coated by γ-PGA showed a significant silencing effect. The binary complexes showed significant cytotoxicity although the ternary complexes coated by γ-PGA did not show significant cytotoxicity. The ternary complexes coated by γ-PGA suppressed luciferase activity in the tumor after their direct injection into the tumors of mice bearing Colon26/Luc cells. Thus, we have newly identified safe and efficient ternary complexes of siRNA for clinical use.