Isocyclosporin A
(Synonyms: 异构环孢菌素A) 目录号 : GC40752
An isomer of cyclosporin A
Cas No.:59865-16-6
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
Isocyclosporin A is an isomer of cyclosporin A that forms upon acid hydrolysis or upon ionization during mass spectrometry (MS). A method to differentiate the two isomers during MS has been described.
| Cas No. | 59865-16-6 | SDF | |
| 别名 | 异构环孢菌素A | ||
| Canonical SMILES | CC(C/C=C/C)C(C(NC)C(NC(CC)C(N(C)CC(N(C)C(CC(C)C)C(NC(C(C)C)C(N(C)C1CC(C)C)=O)=O)=O)=O)=O)OC(C(C(C)C)N(C)C(C(CC(C)C)N(C)C(C(CC(C)C)N(C)C(C(C)NC(C(C)NC1=O)=O)=O)=O)=O)=O | ||
| 分子式 | C62H111N11O12 | 分子量 | 1202.6 |
| 溶解度 | DMF: Soluble,DMSO: Soluble,Ethanol: Soluble,Methanol: Soluble | 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 | 0.8315 mL | 4.1577 mL | 8.3153 mL |
| 5 mM | 0.1663 mL | 0.8315 mL | 1.6631 mL |
| 10 mM | 0.0832 mL | 0.4158 mL | 0.8315 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。
Differentiation of cyclosporin A from Isocyclosporin A by liquid chromatography/electrospray ionization mass spectrometry with post-column addition of divalent metal salt
Rapid Commun Mass Spectrom 2014 Mar 15;28(5):465-70.PMID:24497284DOI:10.1002/rcm.6805.
Rationale: Cyclosporin A (CsA) rearranges to its isomer Isocyclosporin A (isoCsA) upon acid hydrolysis and also during ionization in the ion source of the mass spectrometer. It has been reported that both compounds could not be differentiated by tandem mass spectrometry (MS/MS) using atmospheric pressure ionization (API) sources and ambiguously differentiated by using other sources. In order to analyze these compounds which are common fungal metabolites, it is relevant to develop a simple method for their differentiation. Methods: CsA and isoCsA were analyzed by liquid chromatography/mass spectrometry (LC/MS) with post-column addition of metal ion solutions in a quadrupole time-of-flight instrument equipped with an electrospray ionization (ESI) source. Results: Mass spectra of CsA obtained upon post-column addition of solutions of Ca(II), Cu(II) and Zn(II) showed complexes between cyclosporin and the metal, including [2CsA + Me](2+) and [CsA-H + Me](+). These complexes were not observed in the spectra of isoCsA. The same results were observed at different metal concentrations. Conclusions: Differentiation via metal complexation in positive ion mode LC/ESI-MS was performed to simultaneously distinguish CsA and its isomer isoCsA.
Kinetics and mechanism of isomerization of cyclosporin A
Pharm Res 1992 May;9(5):617-22.PMID:1608891DOI:10.1023/a:1015841824760.
The kinetics of isomerization of cyclosporin A to Isocyclosporin A were studied in various nonaqueous solvents as a function of temperature and added methanesulfonic acid. The rate of isomerization was found to be acid-catalyzed over the acid concentration range studied. The choice of organic solvent significantly altered the rate of isomerization. For a series of alcohols, the rate was enhanced with increasing dielectric constant of the media, however, this correlation did not hold upon introduction of the dipolar aprotic solvent, tetrahydrofuran. Conversion of cyclosporin A to Isocyclosporin A in tetrahydrofuran was found to contain diminished side reactions as compared to alcoholic solvents. The rate of conversion of Isocyclosporin A to cyclosporin A was determined in aqueous buffers as a function of pH, buffer concentration, and temperature. The rates of conversion were extremely rapid compared to the forward reaction. Based on the pH dependencies of dilute solution reactivities, Isocyclosporin A displayed a kinetically generated pKa value of 6.9 for the secondary amine moiety. From pH 8 to pH 10 the pH-rate profile plot is linear, with a slope approximately equal to unity, indicating apparent hydroxide ion catalysis. The break in pH-rate profile suggests a change in the rate-determining step upon protonation of Isocyclosporin A. The rate of isomerization in plasma was comparable with that found in a pH 7.4 buffer solution, indicating that plasma proteins do not significantly alter the isomerization kinetics of Isocyclosporin A to cyclosporin A.
Kinetics of acid-catalyzed degradation of cyclosporin A and its analogs in aqueous solution
Int J Pept Protein Res 1994 Mar;43(3):239-47.PMID:8005746DOI:10.1111/j.1399-3011.1994.tb00386.x.
The kinetics and mechanism of the degradation of cyclosporin A have been studied under aqueous acidic conditions. The rate of degradation was found to be specific acid-catalyzed over the pH range studied (1-4), with Isocyclosporin A as the predominant degradation product. Selective reduction of the olefinic bond of the amino acid 2-N-methyl-(R)-((E)-2-butenyl)-4-methyl-L-threonine (MeBmt) did not affect the overall degradation kinetics and product distribution of cyclosporin A. These observations indicate that the alternative degradation pathway involving intramolecular alkoxy addition to the olefinic bond of amino acid MeBmt apparently does not significantly contribute to the overall degradation kinetics of cyclosporin A in the pH range 1-4. The chemical reactivity of O-acetyl-cyclosporin A was examined to probe the governing mechanism for the isomerization of cyclosporin A. Under identical conditions, O-acetyl-cyclosporin A showed a much greater chemical stability than cyclosporin A, consistent with a mechanism involving the hydroxyoxazolidine intermediate. The chemical stability of cyclosporin C, which contains two beta-hydroxyl groups, was also examined. The rate and product distribution for the degradation of cyclosporin C suggest that under aqueous acidic conditions it undergoes N,O-acyl migration solely at the amino acid residue MeBmt. Additionally, the impact of side-chain bulkiness of amino acid MeBmt was examined by studying the degradation kinetics of a series of cyclosporin A analogs.(ABSTRACT TRUNCATED AT 250 WORDS)
Synthesis of a fluorescent derivative of cyclosporin A for high-performance liquid chromatography analysis
J Pharm Sci 1991 Apr;80(4):363-7.PMID:1865337DOI:10.1002/jps.2600800416.
A direct assay method for use in studies of cyclosporin binding must be highly sensitive and selective since it must be capable of measuring the concentrations encountered in the protein-free matrix. The failure of current HPLC methods to achieve the sensitivity required for binding studies may be attributed to the use of UV detection, which relies on the relatively weak end-absorption of cyclosporin A. A method involving fluorescence derivatization was sought with the aim of increasing HPLC assay sensitivity. A method is described for producing a fluorescent derivative of cyclosporin A, a compound which has no functional groups which are easily derivatized. However, intramolecular rearrangement of cyclosporin A to form its structural isomer, Isocyclosporin A, exposes a secondary amine which can be reacted with dansyl chloride to produce a fluorescent derivative. This two-step derivatization procedure was used as the basis of an HPLC fluorescence assay. Although this assay is not sufficiently sensitive to measure concentrations encountered in the protein-free matrix during plasma binding studies, the method does point to the possible development of a more sensitive assay using a derivatizing reagent other than dansyl chloride.
Separating Isomers, Conformers, and Analogues of Cyclosporin using Differential Mobility Spectroscopy, Mass Spectrometry, and Hydrogen-Deuterium Exchange
Anal Chem 2020 Aug 18;92(16):11053-11061.PMID:32698568DOI:10.1021/acs.analchem.0c00191.
Cyclosporins are an invaluable class of drug used to prevent the rejection of transplanted tissue. While the most popular drug in this group is cyclosporin A, several other analogues are available, including some enantiomeric and structurally isomeric forms. Unfortunately, the presence of such isomers can make the detection and identification of these drugs by mass spectrometry (MS) alone quite challenging. Here, we demonstrate the separation and analysis of six cyclosporin analogues using liquid chromatography (LC) and differential mobility spectroscopy (DMS) coupled to MS. Using DMS, we demonstrate the separation of three isomers: CycA and CycH (cyclosporin H), which are enantiomers, and Isocyclosporin A (a structural isomer of CycA and CycH). For several of the cyclosporins, we can separate different conformers for each isomeric form. After DMS separation, tandem mass spectrometry (MS/MS) analyses of the separated isomers also distinguish these isomeric forms of cyclosporin. In addition, we have probed differences between each isomer by using gas-phase hydrogen-deuterium exchange (HDX) immediately after DMS separation, which reveals differences in the levels of intramolecular hydrogen bonding between each of the cyclosporins.