Swinholide A
目录号 : GC44976An actin depolymerizing macrolide
Cas No.:95927-67-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >97.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Swinholide A is a natural dimeric dilactone macrolide toxin that causes actin depolymerization in cells. [1] [2] It stabilizes actin dimers and also binds to and severs F-actin filaments.[1] [3] Swinholide A binds to G-actin in a 1:2 molar ratio and decreases the rate of nucleotide exchange in G-actin. [2]
Reference:
[1]. Bubb, M.R., Spector, I., Bershadsky, A.D., et al. Swinholide A is a microfilament disrupting marine toxin that stabilizes actin dimers and severs actin filaments. The Journal of Biological Chemisty 270(8), 3463-3466 (1995).
[2]. Saito, S.y., Watabem, S., Ozaki, H., et al. Actin-depolymerizing effect of dimeric macrolides, bistheonellide A and swinholide A. Journal of Biochemistry 123(4), 571-578 (1998).
[3]. Terry, D.R., Higa, T., and Bubb, M.R. Misakinolide A is a marine macrolide that caps but does not sever filamentous actin. The Journal of Biological Chemisty 272(12), 7841-7845 (1997)
| Cas No. | 95927-67-6 | SDF | |
| 化学名 | (1R,3S,5E,7E,11S,12S,13R,15S,16S,17S,19S,23R,25S,27E,29E,33S,34S,35R,37S,38S,39S,41S)-3,13,15,25,35,37-hexahydroxy-11,33-bis[(1S,2S,3S)-2-hydroxy-1,3-dimethyl-5-[(2S,4R,6S)-tetrahydro-4-methoxy-6-methyl-2H-pyran-2-yl]pentyl]-17,39-dimethoxy-6,12,16,28,34,38-hexamethyl-10,32,45,46-tetraoxatricyclo[39.3.1.119,23]hexatetraconta-5,7,21,27,29,43-hexaene-9,31-dione | ||
| Canonical SMILES | C[C@@H]([C@H]([C@H](CC[C@@H]1O[C@H](C[C@@H](OC)C1)C)C)O)C([C@@H](C)[C@H](O)C[C@H](O)[C@H](C)[C@@H](OC)C[C@]2(O[C@@]([H])(C=CC2)C[C@@H](O)C/C=C(C)/C=C/C(OC([C@H]3C)[C@H]([C@H]([C@H](CC[C@@H]4O[C@H](C[C@@H](OC)C4)C)C)O)C)=O)[H])OC(/C=C/C(C)=C/C[C@H](O) | ||
| 分子式 | C78H132O20 | 分子量 | 1389.9 |
| 溶解度 | Soluble in methanol, ethanol, DMSO | 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 | 0.7195 mL | 3.5974 mL | 7.1948 mL |
| 5 mM | 0.1439 mL | 0.7195 mL | 1.439 mL |
| 10 mM | 0.0719 mL | 0.3597 mL | 0.7195 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。
Structure-activity relationship studies on an antitumor marine macrolide using aplyronine a-swinholide A hybrid
Org Biomol Chem 2022 Apr 6;20(14):2922-2938.PMID:35322840DOI:10.1039/d2ob00118g.
An aplyronine A-swinholide A hybrid, consisting of the macrolactone part of aplyronine A and the side chain part of Swinholide A, was designed, synthesized, and biologically evaluated. This hybrid induced protein-protein interactions between two major cytoskeletal proteins actin and tubulin in the same manner as aplyronine A, and exhibited potent cytotoxicity and actin-depolymerizing activity. The importance of the methoxy group in the N,N,O-trimethylserine ester was clarified by the structure-activity relationship studies of the amino acid moiety by using the hybrid analogs. Furthermore, the comparison of the actin-depolymerizing activities between the side chain analogs of aplyronine A and Swinholide A showed that the side chain analog of Swinholide A had much weaker actin-depolymerizing activity than that of aplyronine A.
Swinholide A is a microfilament disrupting marine toxin that stabilizes actin dimers and severs actin filaments
J Biol Chem 1995 Feb 24;270(8):3463-6.PMID:7876075DOI:10.1074/jbc.270.8.3463.
Swinholide A, isolated from the marien sponge Theonella swinhoei, is a 44-carbon ring dimeric dilactone macrolide with a 2-fold axis of symmetry. Recent studies have elucidated its unusual structure and shown that it has potent cytotoxic activity. We now report that Swinholide A disrupts the actin cytoskeleton of cells grown in culture, sequesters actin dimers in vitro in both polymerizing and non-polymerizing buffers with a binding stoichiometry of one Swinholide A molecule per actin dimer, and rapidly severs F-actin in vitro with high cooperativity. These unique properties are sufficient to explain the cytotoxicity of Swinholide A. They also suggest that Swinholide A might be a model for studies of the mechanism of action of F-actin severing proteins and be therapeutically useful in conditions where filamentous actin contributes to pathologically high viscosities.
The Swinholide Biosynthesis Gene Cluster from a Terrestrial Cyanobacterium, Nostoc sp. Strain UHCC 0450
Appl Environ Microbiol 2018 Jan 17;84(3):e02321-17.PMID:29150506DOI:10.1128/AEM.02321-17.
Swinholides are 42-carbon ring polyketides with a 2-fold axis of symmetry. They are potent cytotoxins that disrupt the actin cytoskeleton. Swinholides were discovered from the marine sponge Theonella sp. and were long suspected to be produced by symbiotic bacteria. Misakinolide, a structural variant of swinholide, was recently demonstrated to be the product of a symbiotic heterotrophic proteobacterium. Here, we report the production of Swinholide A by an axenic strain of the terrestrial cyanobacterium Nostoc sp. strain UHCC 0450. We located the 85-kb trans-AT polyketide synthase (PKS) swinholide biosynthesis gene cluster from a draft genome of Nostoc sp. UHCC 0450. The swinholide and misakinolide biosynthesis gene clusters share an almost identical order of catalytic domains, with 85% nucleotide sequence identity, and they group together in phylogenetic analysis. Our results resolve speculation around the true producer of swinholides and demonstrate that bacteria belonging to two distantly related phyla both produce structural variants of the same natural product. In addition, we described a biosynthesis cluster from Anabaena sp. strain UHCC 0451 for the synthesis of the cytotoxic and antifungal scytophycin. All of these biosynthesis gene clusters were closely related to each other and created a group of cytotoxic macrolide compounds produced by trans-AT PKSs of cyanobacteria and proteobacteria.IMPORTANCE Many of the drugs in use today originate from natural products. New candidate compounds for drug development are needed due to increased drug resistance. An increased knowledge of the biosynthesis of bioactive compounds can be used to aid chemical synthesis to produce novel drugs. Here, we show that a terrestrial axenic culture of Nostoc cyanobacterium produces swinholides, which have been previously found only from marine sponge or samples related to them. Swinholides are polyketides with a 2-fold axis of symmetry, and they are potent cytotoxins that disrupt the actin cytoskeleton. We describe the biosynthesis gene clusters of swinholide from Nostoc cyanobacteria, as well as the related cytotoxic and antifungal scytophycin from Anabaena cyanobacteria, and we study the evolution of their trans-AT polyketide synthases. Interestingly, swinholide is closely related to misakinolide produced by a symbiotic heterotrophic proteobacterium, demonstrating that bacteria belonging to two distantly related phyla and different habitats can produce similar natural products.
Swinholide J, a potent cytotoxin from the marine sponge Theonella swinhoei
Mar Drugs 2011;9(6):1133-1141.PMID:21747751DOI:10.3390/md9061133.
In our ongoing search for new pharmacologically active leads from Solomon organisms, we have examined the sponge Theonella swinhoei. Herein we report the isolation and structure elucidation of Swinholide A (1) and one new macrolide, swinholide J (2). Swinholide J is an unprecedented asymmetric 44-membered dilactone with an epoxide functionality in half of the molecule. The structural determination was based on extensive interpretation of high-field NMR spectra and HRESIMS data. Swinholide J displayed potent in vitro cytotoxicity against KB cells (human nasopharynx cancer) with an IC(50) value of 6 nM.
Structural basis of Swinholide A binding to actin
Chem Biol 2005 Mar;12(3):287-91.PMID:15797212DOI:10.1016/j.chembiol.2005.02.011.
Marine toxins targeting the actin cytoskeleton represent a new and promising class of anti-cancer compounds. Here we present a 2.0 A resolution structure of Swinholide A, a marine macrolide, bound to two actin molecules. The structure demonstrates that the actin dimer in the complex does not represent a physiologically relevant entity, for the two actin molecules do not interact with each other. The Swinholide A actin binding site is the same as that targeted by toxins of the trisoxazole family and numerous actin binding proteins, highlighting the importance of this site in actin polymerization. The observed structure reveals the mechanism of action of Swinholide A and provides a structural framework about which to design new agents directed at the cytoskeleton.