Territrem B
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| Category | Enzyme inhibitors |
| Catalog number | BBF-04350 |
| CAS | 70407-20-4 |
| Molecular Weight | 526.57 |
| Molecular Formula | C29H34O9 |
| Purity | ≥95% |
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Description
Territrem B is a mycotoxin originally isolated from Aspergillus terreus that irreversibly inhibits acetylcholinesterase (AChE).
Specification
| Synonyms | (4aR,6aR,12aS,12bS)-4a,6,6a,12,12a,12b-Hexahydro-4a,12a-dihydroxy-4,4,6a,12b-tetramethyl-9-(3,4,5-trimethoxyphenyl)-4H,11H-naphtho[2,1-b]pyrano[3,4-e]pyran-1,11(5H)-dione; [4aR-(4aα,6aβ,12aα,12bβ)]-4a,6,6a,12,12a,12b-Hexahydro-4a,12a-dihydroxy-4,4,6a,12b-tetramethyl-9-(3,4,5-trimethoxyphenyl)-4H,11H-naphtho[2,1-b]pyrano[3,4-e]pyran-1,11(5H)-dione |
| Storage | Store at -20°C |
| IUPAC Name | (1S,2S,7R,10R)-1,7-dihydroxy-2,6,6,10-tetramethyl-14-(3,4,5-trimethoxyphenyl)-11,15-dioxatetracyclo[8.8.0.02,7.012,17]octadeca-4,12(17),13-triene-3,16-dione |
| Canonical SMILES | CC1(C=CC(=O)C2(C1(CCC3(C2(CC4=C(O3)C=C(OC4=O)C5=CC(=C(C(=C5)OC)OC)OC)O)C)O)C)C |
| InChI | InChI=1S/C29H34O9/c1-25(2)9-8-22(30)27(4)28(25,32)11-10-26(3)29(27,33)15-17-19(38-26)14-18(37-24(17)31)16-12-20(34-5)23(36-7)21(13-16)35-6/h8-9,12-14,32-33H,10-11,15H2,1-7H3/t26-,27+,28-,29-/m1/s1 |
| InChI Key | PBXNNDFKPQPJBB-VJLHXPKFSA-N |
| Source | Territrem B is a tremorgenic mycotoxin found in the fungus Aspergillus terreus. |
Properties
| Appearance | Solid Powder |
| Boiling Point | 693.0±55.0°C at 760 mmHg |
| Melting Point | 200-203°C |
| Density | 1.4±0.1 g/cm3 |
| Solubility | Soluble in DMSO |
Toxicity
| Carcinogenicity | No indication of carcinogenicity to humans (not listed by IARC). |
| Mechanism Of Toxicity | Territrem B is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen. |
Reference Reading
1. Isolation, chemical structure, acute toxicity, and some physicochemical properties of territrem C from Aspergillus terreus
C M Yang, C K Yang, K H Ling, H H Liou Appl Environ Microbiol . 1984 Jan;47(1):98-100. doi: 10.1128/aem.47.1.98-100.1984.
Territrem C, a new tremorgenic mycotoxin (C28H32O9; molecular weight, 512.20) was isolated from the chloroform extract of rice cultures of Aspergillus terreus 23-1, which also produces territrems A and B. Isolation, acute toxicity, and some physicochemical properties of territrem C are discussed in this paper. The spectral and chemical evidence indicated that the structural difference between territrem C and territrem B (C29H34O9) was in their phenyl moieties: a 4-hydroxy-3,5-dimethoxy phenyl group in territrem C and a 3,4,5-trimethoxy phenyl group in territrem B. It was also demonstrated that territrem B was obtained by methylation of territrem C with dimethyl sulfate.
2. Territrem B, a tremorgenic mycotoxin that inhibits acetylcholinesterase with a noncovalent yet irreversible binding mechanism
F C Peng, Y L Luo, J W Chen, M J Hwang, K H Ling J Biol Chem . 1999 Dec 3;274(49):34916-23. doi: 10.1074/jbc.274.49.34916.
Territrem B (TRB) is a fungal metabolite isolated from Aspergillus terreus shown previously to be a potent and irreversible inhibitor of acetylcholinesterase (AChE). In the present study, a number of binding and inhibition assays were carried out to further characterize the inhibitory effect of TRB. The results indicate that the binding of TRB (a) is much more selective than a well characterized selective inhibitor of AChE, BW284C51, (b) adopts a one-to-one stoichiometry with the enzyme, (c) cannot be undone by an AChE-regenerating oxime agent, which contrasts the ability of 8 M urea to release AChE-bound TRB, (d) is enhanced by high concentration NaCl but prevented, unless preincubated, by Triton X-100, and (e) exhibits quasi-first order kinetics with an overall inhibition constant of 0.01 nM(-1) min(-1). Together these results suggest a very different irreversible binding (a noncovalent type) from that of the covalent type, which involves typical irreversible AChE inhibitors such as diisopropylfluorophosphate and neostigmine. According to the prediction of a molecular modeling study, the distinct AChE inhibitory characteristics of TRB may arise from the inhibitor being noncovalently trapped within a unique active-site gorge structure of the enzyme. It was predicted that an optimal TRB. AChE binding would position a narrowing connection of the TRB structure at a constricted area near the entrance of the gorge, thereby providing a structural basis for the observed irreversible binding.
3. Structures of human acetylcholinesterase bound to dihydrotanshinone I and territrem B show peripheral site flexibility
Terrone L Rosenberry, Kazuro Shiomi, Jonah Cheung, Ebony N Gary ACS Med Chem Lett . 2013 Sep 23;4(11):1091-6. doi: 10.1021/ml400304w.
Acetylcholinesterase is a critical enzyme that regulates neurotransmission by degrading the neurotransmitter acetylcholine in synapses of the nervous system. It is an important target for both therapeutic drugs that treat Alzheimer's disease and chemical warfare agents that cripple the nervous system and cause death through paralysis. The enzyme has both catalytic and peripheral sites to which inhibitors may bind. Structures of recombinant human acetylcholinesterase in complex with the natural product inhibitors dihydrotanshinone I and territrem B reveal dihydrotanshinone I binding that is specific to only the peripheral site and territrem B binding that spans both sites and distorts the protein backbone in the peripheral site. These inhibitors may function as important molecular templates for therapeutics used for treatment of disease and protection against nerve agents.
Spectrum
Predicted LC-MS/MS Spectrum - 10V, Positive
Experimental Conditions
Ionization Mode: Positive
Collision Energy: 10 eV
Instrument Type: QTOF (generic), spectrum predicted by CFM-ID
Mass Resolution: 0.0001 Da
Molecular Formula: C29H34O9
Molecular Weight (Monoisotopic Mass): 526.2203 Da
Molecular Weight (Avergae Mass): 526.5749 Da
Collision Energy: 10 eV
Instrument Type: QTOF (generic), spectrum predicted by CFM-ID
Mass Resolution: 0.0001 Da
Molecular Formula: C29H34O9
Molecular Weight (Monoisotopic Mass): 526.2203 Da
Molecular Weight (Avergae Mass): 526.5749 Da
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
