Name: ALPHA-AMANITIN
Brand: BOC Sciences
Rating: 5 (1 reviews)

Synonyms

α-Amatoxin; cyclo[L-Asparaginyl-4-hydroxy-L-proly-(R-4,5-dihydroxy-L-isoleucyl-6-hydroxy-2-mercapto-L-tryptophylglycyl-L-isoleucylglycyl-L-cysteinyl]cyclic (4-8)-sulfide (R)-S-oxide

IUPAC Name

2-[(1R,4S,8R,10S,13S,16S,34S)-34-[(2S)-butan-2-yl]-13-[(2R,3R)-3,4-dihydroxybutan-2-yl]-8,22-dihydroxy-2,5,11,14,27,30,33,36,39-nonaoxo-27λ4-thia-3,6,12,15,25,29,32,35,38-nonazapentacyclo[14.12.11.06,10.018,26.019,24]nonatriaconta-18(26),19(24),20,22-tetraen-4-yl]acetamide

Canonical SMILES

CCC(C)C1C(=O)NCC(=O)NC2CS(=O)C3=C(CC(C(=O)NCC(=O)N1)NC(=O)C(NC(=O)C4CC(CN4C(=O)C(NC2=O)CC(=O)N)O)C(C)C(CO)O)C5=C(N3)C=C(C=C5)O

InChI

InChI=1S/C39H54N10O14S/c1-4-16(2)31-36(60)42-11-29(55)43-25-15-64(63)38-21(20-6-5-18(51)7-22(20)46-38)9-23(33(57)41-12-30(56)47-31)44-37(61)32(17(3)27(53)14-50)48-35(59)26-8-19(52)13-49(26)39(62)24(10-28(40)54)45-34(25)58/h5-7,16-17,19,23-27,31-32,46,50-53H,4,8-15H2,1-3H3,(H2,40,54)(H,41,57)(H,42,60)(H,43,55)(H,44,61)(H,45,58)(H,47,56)(H,48,59)/t16-,17-,19+,23-,24-,25-,26-,27-,31-,32-,64?/m0/s1

InChIKey

CIORWBWIBBPXCG-JAXJKTSHSA-N

Density

1.163 g/cm3 (Predicted)

Solubility

Soluble in Water

Melting Point

254-255 °C

Flash Point

934.9°C

Index Of Refraction

1.694

Optical Rotation

SPECIFIC OPTICAL ROTATION: +191 DEG at 20 °C/D; MAX ABSORPTION: 302 NM

PSA

400.09000

Source

It is found in several members of the Amanita genus of mushrooms, one being the Death cap (Amanita phalloides) as well as the Destroying angel, a complex of similar species, principally A. virosa and A. bisporigera. It is also found in the mushrooms Galerina marginata and Conocybe filaris.

Appearance

Acicular Crystal

Quantity

Data not available, please inquire.

Shelf Life

2 years

Shipping

Room temperature

Storage

Store at -20°C

Pictograms

Health Hazard; Acute Toxic

Signal Word

Danger

Boiling Point

1622.2±65.0 °C (Predicted)

Form

Solid

In Vitro

Alpha-Amanitin decreases TAF15 mRNA and TAF15 protein levels in MKN45 cells, and inhibits the RNAPII activity towards TAF15 mRNA. alpha-Amanitin decreases cell viability by 14%, 21%, 41%, 44%, and 50% at concentrations of 100, 10, 1, 0.1, and 0.01 µg/mL, respectively. The LD50 of the alpha-Amanitin at 36 h is measured as 1 µg/mL. The total amount of protein within the cell at 24 h is significantly increased for the 1 µg/mL dose of alpha-Amanitin compared to the control. Alpha-Amanitin dramatically decreases the expression of gap junctional genes (Gja1, Gja4 and Gjc1) and gonadotropin receptor genes (FSHr and LHr) in cumulus cells.

In Vivo

The intravenous LD50 dose of alpha-Amanitin is 0.327 mg/kg body weight after intravenous injection into BALB/c mice. After 12 h of alpha-Amanitin injection in caudal vein, the levels of WBC, RBC and HGB decrease significantly, while those of BUN and Crea increase significantly in serum. alpha-Amanitin inhibits some genes (Hsp90b1, Irx4, etc.), whose encoded proteins regulate the RNA polymerase II activity. alpha-Amanitin down-regulates some proteins (Nmi, Trpc5, etc.) taking part in the transcription progress. alpha-Amanitin has potent activity in DTC suppression. Mice injected with alpha-Amanitin (0.4 mg/kg, i.p.)-treated cells maintain their body weight, while those receiving a peritoneal injection of MKN45 cells show a constant decrease in body weight.

Mechanism Of Action

In Comparison With The Phallotoxins/...The Long Delayed Hepatotoxic Response Seen In Human Poisonings...Is More Likely Due To...Alpha-, Beta-, & Gamma-Amanitin, Especially The Alpha Component. These So-Called Amatoxins...Are More Toxic Than The Phallotoxins, &, Unlike The Latter, They Damage The Nucleolus & Later The Nucleus Of Liver Cells.

Alpha-Amanitin, a potent toxin derived from select mushrooms, notably the Amanita species, possesses diverse applications. Here are four key uses of Alpha-Amanitin, expressed with high perplexity and burstiness:

Cancer Research: Employed in cancer studies, Alpha-Amanitin targets RNA polymerase II, a pivotal enzyme in mRNA synthesis within eukaryotic cells. By halting this critical process, Alpha-Amanitin disrupts cell transcription, offering insights into cancer cell biology and therapeutic possibilities. Researchers leverage its potent inhibitory nature to unravel mechanisms of tumor cell survival and pinpoint novel drug targets amidst the intricate realm of oncology research.

Toxinology: Serving as a cornerstone in toxinology investigations, Alpha-Amanitin sheds light on the toxic effects and mechanisms of mushroom-induced poisonings. Thorough scrutiny of its impact on human physiology aids in the development of diagnostic tools and treatment strategies for cases of mushroom poisoning. The knowledge garnered from these explorations plays a vital role in enhancing public health responses to incidents of mushroom-related toxicities, ensuring proactive intervention and management.

Molecular Biology: Functioning as a valuable research tool, Alpha-Amanitin selectively blocks RNA polymerase II, enabling the study of gene transcription processes. By precisely impeding mRNA synthesis, researchers dissect the functions of diverse genes and regulatory components, contributing to a deeper comprehension of gene expression dynamics, RNA processing intricacies, and various cellular functions. This nuanced exploration is pivotal in expanding our understanding of the intricate molecular mechanisms governing life.

Pharmaceutical Development: Within the realm of therapeutic agent discovery, Alpha-Amanitin offers a template for investigating enzyme inhibitors that modulate gene expression. While its inherent toxicity poses a challenge, researchers are exploring modified derivatives of Alpha-Amanitin with reduced adverse effects for potential therapeutic applications. This innovative research endeavors to harness the potent inhibitory effects of Alpha-Amanitin while mitigating potential drawbacks, paving the way for novel therapeutic interventions grounded in molecular pharmacology.

1.RNA and protein synthesis is required for Ancylostoma caninum larval activation.

Dryanovski DI;Dowling C;Gelmedin V;Hawdon JM Vet Parasitol. 2011 Jun 30;179(1-3):137-43. doi: 10.1016/j.vetpar.2011.01.062. Epub 2011 Feb 26.

The developmentally arrested infective larva of hookworms encounters a host-specific signal during invasion that initiates the resumption of suspended developmental pathways. The resumption of development during infection is analogous to recovery from the facultative arrested dauer stage in the free-living nematode Caenorhabditis elegans. Infective larvae of the canine hookworm Ancylostoma caninum resume feeding and secrete molecules important for infection when exposed to a host mimicking signal in vitro. This activation process is a model for the initial steps of the infective process. Dauer recovery requires protein synthesis, but not RNA synthesis in C. elegans. To determine the role of RNA and protein synthesis in hookworm infection, inhibitors of RNA and protein synthesis were tested for their effect on feeding and secretion by A. caninum infective larvae. The RNA synthesis inhibitors α-amanitin and actinomycin D inhibit feeding dose-dependently, with IC(50) values of 30 and 8 μM, respectively. The protein synthesis inhibitors puromycin (IC(50)=110 μM), cycloheximide (IC(50)=50 μM), and anisomycin (IC(50)=200 μM) also displayed dose-dependent inhibition of larval feeding. Significant inhibition of feeding by α-amanitin and anisomycin occurred when the inhibitors were added before 12h of the activation process, but not if the inhibitors were added after 12h.

2.Lamin A/C speckles mediate spatial organization of splicing factor compartments and RNA polymerase II transcription.

Kumaran RI;Muralikrishna B;Parnaik VK J Cell Biol. 2002 Dec 9;159(5):783-93. Epub 2002 Dec 9.

The A-type lamins have been observed to colocalize with RNA splicing factors in speckles within the nucleus, in addition to their typical distribution at the nuclear periphery. To understand the functions of lamin speckles, the effects of transcriptional inhibitors known to modify RNA splicing factor compartments (SFCs) were examined. Treatment of HeLa cells with alpha-amanitin or 5,6-dichlorobenzimidazole riboside (DRB) inhibited RNA polymerase II (pol II) transcription and led to the enlargement of lamin speckles as well as SFCs. Removal of the reversible inhibitor DRB resulted in the reactivation of transcription and a rapid, synchronous redistribution of lamins and splicing factors to normal-sized speckles, indicating a close association between lamin speckles and SFCs. Conversely, the expression of NH2-terminally modified lamin A or C in HeLa cells brought about a loss of lamin speckles, depletion of SFCs, and down-regulation of pol II transcription without affecting the peripheral lamina. Our results suggest a unique role for lamin speckles in the spatial organization of RNA splicing factors and pol II transcription in the nucleus.

3.Determination of alpha-, beta-, and gamma-amanitin by high performance thin-layer chromatography in Amanita phalloides (Vaill. ex Fr.) secr. from various origin.

Stijve T;Seeger T Z Naturforsch C. 1979 Dec;34(12):1133-8.

A fast, sensitive high performance thin-layer chromatographic method for the determination of alpha-, beta-, and gamma-amanitin in crude, methanolic extracts of Amanita phalloides is described. The limit of detection is 50 ng of each amanitin. With this method amanitin was determined in 24 pooled samples of Amanita phalloides, collected between 1970 and 1977 in Germany and Switzerland. The total amanitin content varied between 2010 and 7300 mg/kg dry weight and the average value was 4430 mg/kg of which 43% was alpha-amanitin, 49% beta-amanitin and 8% gamma-amanitin. The origin of the fungi hardly influenced their amanitin content: in samples collected during the same year at different sites it fluctuated within a factor of 1.7. The amanitin content of samples from the same site, but collected in different years, maximally varied within a factor of 3.7. The partial decomposition of amanitins during prolonged storage of the lyophilized samples undoubtedly contributed to this variation. Phalloidin, which was determined by conventional thin-layer-chromatography, could not be detected in a sample from 1970, whereas its concentration in material collected during 1977 amounted to 2400 mg/kg dry weight.

Catalog	Product Name	CAS
BADC-00604	Mal-C6-α-Amanitin	1578249-76-9
BADC-00822	γ-Amanitin	21150-23-2
BADC-00823	ε-Amanitin	21705-02-2
BADC-01363	Dideoxy-amanitin	58255-46-2
BADC-00733	MC-vc-PAB-C6-a-amanitin