Aureobasidin A
(Synonyms: 巴西芬净,Basifungin) 目录号 : GC62854
Aureobasidin A (Basifungin) 是一种环状肽、是抗真菌的抗生素。Aureobasidin A (Basifungin) 是肌醇磷酸化神经酰胺合成酶 AUR1 的抑制剂。
Cas No.:127785-64-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Aureobasidin A (Basifungin), a cyclic depsipetide, is an antifungal antibiotic. Aureobasidin A (Basifungin) A is an inhibitor of the inositolphosphorylceramide synthase AUR1[1][2].
Aureobasidin A arrests growth of yeast cells through both ceramide intoxication and deprivation of essential inositolphosphorylceramides[2].
[1]. K Ikai, et al. Structure of aureobasidin A. J Antibiot (Tokyo). 1991 Sep;44(9):925-33.
[2]. Vanessa Cerantola, et al. Aureobasidin A arrests growth of yeast cells through both ceramide intoxication and deprivation of essential inositolphosphorylceramides. Mol Microbiol. 2009 Mar;71(6):1523-37.
[3]. K Kino, et al. Aureobasidin A, an antifungal cyclic depsipeptide antibiotic, is a substrate for both human MDR1 and MDR2/P-glycoproteins. FEBS Lett. 1996 Dec 9;399(1-2):29-32.
| Cas No. | 127785-64-2 | SDF | |
| 别名 | 巴西芬净,Basifungin | ||
| 分子式 | C60H92N8O11 | 分子量 | 1101.42 |
| 溶解度 | DMSO : 100 mg/mL (90.79 mM; Need ultrasonic) | 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 | 0.9079 mL | 4.5396 mL | 9.0792 mL |
| 5 mM | 0.1816 mL | 0.9079 mL | 1.8158 mL |
| 10 mM | 0.0908 mL | 0.454 mL | 0.9079 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。
Solution cis-Proline Conformation of IPCs Inhibitor Aureobasidin A Elucidated via NMR-Based Conformational Analysis
J Nat Prod 2022 Jun 24;85(6):1449-1458.PMID:35622967DOI:10.1021/acs.jnatprod.1c01071.
Aureobasidin A (abA) is a natural depsipeptide that inhibits inositol phosphorylceramide (IPC) synthases with significant broad-spectrum antifungal activity. abA is known to have two distinct conformations in solution corresponding to trans- and cis-proline (Pro) amide bond rotamers. While the trans-Pro conformation has been studied extensively, cis-Pro conformers have remained elusive. Conformational properties of cyclic peptides are known to strongly affect both potency and cell permeability, making a comprehensive characterization of abA conformation highly desirable. Here, we report a high-resolution 3D structure of the cis-Pro conformer of Aureobasidin A elucidated for the first time using a recently developed NMR-driven computational approach. This approach utilizes ForceGen's advanced conformational sampling of cyclic peptides augmented by sparse distance and torsion angle constraints derived from NMR data. The obtained 3D conformational structure of cis-Pro abA has been validated using anisotropic residual dipolar coupling measurements. Support for the biological relevance of both the cis-Pro and trans-Pro abA configurations was obtained through molecular similarity experiments, which showed a significant 3D similarity between NMR-restrained abA conformational ensembles and another IPC synthase inhibitor, pleofungin A. Such ligand-based comparisons can further our understanding of the important steric and electrostatic characteristics of abA and can be utilized in the design of future therapeutics.
A critical role of farnesol in the modulation of Amphotericin B and Aureobasidin A antifungal drug susceptibility
Mycology 2022 Oct 28;13(4):305-317.PMID:36405337DOI:10.1080/21501203.2022.2138599.
Candida albicans and its related species can cause opportunistic infections such as "candidiasis" in immunocompromised individuals with a high morbidity and mortality rate. Several antifungal drugs available in the market are often used to treat infections caused by pathogenic fungi. However, in fungi, the development of resistance against these drugs quickly evolved. Candida is a dimorphic fungus that can switch between yeast to hyphae form, requires an active biosynthesis of membrane constituents. Sphingolipid and ergosterol molecules, are the major fungal plasma membrane components, and their interaction with the antifungal drug can modulate drug susceptibility. A lipophilic compound farnesol acts as a quorum-sensing molecule synthesised by the isoprenoid biosynthesis pathway in the fungal pathogen Candida. Farnesol is secreted in a cell density-dependent manner inhibits hyphae germination and biofilm formation. In this study, we have investigated whether the farnesol molecules affect the drug susceptibility of the antifungal drug Amphotericin B (AmB) which mainly binds with ergosterol, and Aureobasidin A (AbA), a complex sphingolipid biosynthesis inhibitor. Our studies revealed that a non-toxic and low concentration of farnesol can reduce the efficacy of AmB and AbA on yeast cells. This reduction is probably through the alteration in the complex sphingolipid biosynthesis and ATP-binding cassette (ABC) type membrane transport activity. These findings may shed light on a new direction to explore the role of lipid molecules in the antifungal drug resistance mechanisms in pathogenic yeast.
Structure of Aureobasidin A
J Antibiot (Tokyo) 1991 Sep;44(9):925-33.PMID:1938614DOI:10.7164/antibiotics.44.925.
Aureobasidin A, a new antifungal antibiotic, was isolated from the culture medium of Aureobasidium pullulans R106. Aureobasidin A was a cyclic depsipeptide consisting of eight alpha-amino acid units and one hydroxy acid unit. The structures of the units were found by acid hydrolysis of the antibiotic to be 2(R)-hydroxy-3(R)-methylpentanoic acid, beta-hydroxy-N-methyl-L-valine, N-methyl-L-valine, L-proline, allo-L-isoleucine, N-methyl-L-phenylalanine, L-leucine, and L-phenyl-alanine. The sequence of the units was identified by NMR and FAB-MS of the products from the alkaline hydrolysis of Aureobasidin A.
Chromosome 1 trisomy confers resistance to Aureobasidin A in Candida albicans
Front Microbiol 2023 Mar 17;14:1128160.PMID:37007527DOI:10.3389/fmicb.2023.1128160.
Introduction: Candida albicans is a prevalent opportunistic human fungal pathogen. However, there are currently very few antifungal treatments available. Inositol phosphoryl ceramide synthase is an essential and fungal-specific protein that also provides a novel and promising antifungal target. Aureobasidin A is a widely used inhibitor of inositol phosphoryl ceramide synthase, however the mechanism of resistance to Aureobasidin A is largely unknown in pathogenic fungi. Methods: Here we investigated how C. albicans adapted to low and high concentrations of Aureobasidin A. Results and discussions: We identified trisomy of chromosome 1 as the predominant mechanism of rapid adaptation. Resistance to Aureobasidin A was unstable because of the inherent instability of aneuploids. Importantly, chromosome 1 trisomy simultaneously regulated genes which were associated with Aureobasidin A resistance that are on this aneuploid chromosome as well as on other chromosomes. Furthermore, the pleiotropic effect of aneuploidy caused altered resistance not only to Aureobasidin A but also to other antifungal drugs including caspofungin and 5-flucytosine. We posit aneuploidy provides a rapid and reversible mechanism of development of drug resistance and cross resistance in C. albicans.
Aureobasidin A, an antifungal cyclic depsipeptide antibiotic, is a substrate for both human MDR1 and MDR2/P-glycoproteins
FEBS Lett 1996 Dec 9;399(1-2):29-32.PMID:8980113DOI:10.1016/s0014-5793(96)01265-3.
The human MDR1 gene encodes the multidrug transporter P-glycoprotein (Pgp). Although the MDR2/Pgp shares about 80% identity at the amino acid level with the MDR1/Pgp, the MDR2/Pgp cannot act as a multidrug transporter. We examined the drug sensitivity of Saccharomyces cerevisiae expressing either the human MDR1/Pgp or MDR2/ Pgp. The human MDR1/Pgp conferred about 4-fold resistance to Aureobasidin A, a cyclic depsipeptide antifungal antibiotic, on the drug-sensitive yeast strains. Interestingly the human MDR2/Pgp also conferred about 2.5-fold resistance to Aureobasidin A. The resistance to Aureobasidin A conferred by the MDR2/Pgp as well as by the MDR1/Pgp was overcome by vinblastine, verapamil, and cyclosporin A, depending on their concentrations, but not by colchicine. Aureobasidin A probably interacts directly with Pgps, because it overcame multidrug resistance of human cells and inhibited azidopine photoaffinity labeling of MDR1/Pgp in human cell membranes. These results suggest the possibility that the human MDR1 and MDR2/Pgps have conserved domain(s) for drug recognition.