p-Ethynylphenylalanine
(Synonyms: 4-乙炔基-L-苯丙氨酸HCL,4-Ethynyl-L-phenylalanine) 目录号 : GC61463
p-Ethynylphenylalanine(4-Ethynyl-L-phenylalanine)是一种高效、选择性的，可逆、竞争性的色氨酸羟化酶(TPH)抑制剂，其Ki值为32.6μM。
Cas No.:278605-15-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
p-Ethynylphenylalanine (4-Ethynyl-L-phenylalanine) is a potent, selective, reversible and competitive inhibitor of tryptophan hydroxylase (TPH), with a Ki of 32.6 μM[1].
p-Ethynylphenylalanine selectively and reversibly inhibits the biosynthesis of serotonin[1].p-Ethynylphenylalanine has a low affinity for various recombinant 5-HT receptors (5-HT1, 5-HT2, 5-HT4, 5-HT5, 5-HT6, and 5-HT7)[1].
p-Ethynylphenylalanine (30 mg/kg; i.p.) decreases in 5-HT and 5-HIAA levels in the rat midbrain but not in tissue[1].p-Ethynylphenylalanine does not inhibit the aromatic amino acid decarboxylase[1]. Animal Model: Male Sprague-Dawley rats (200 g)[1]
[1]. Stokes AH, et al. p-ethynylphenylalanine: a potent inhibitor of tryptophan hydroxylase. J Neurochem. 2000 May;74(5):2067-73.
| Cas No. | 278605-15-5 | SDF | |
| 别名 | 4-乙炔基-L-苯丙氨酸HCL,4-Ethynyl-L-phenylalanine | ||
| Canonical SMILES | N[C@@H](CC1=CC=C(C#C)C=C1)C(O)=O | ||
| 分子式 | C11H11NO2 | 分子量 | 189.21 |
| 溶解度 | DMSO: 2.22 mg/mL (11.73 mM) | 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 | 5.2851 mL | 26.4257 mL | 52.8513 mL |
| 5 mM | 1.057 mL | 5.2851 mL | 10.5703 mL |
| 10 mM | 0.5285 mL | 2.6426 mL | 5.2851 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。
p-Ethynylphenylalanine: a potent inhibitor of tryptophan hydroxylase
J Neurochem 2000 May;74(5):2067-73.PMID:10800950DOI:10.1046/j.1471-4159.2000.0742067.x.
Tryptophan hydroxylase (TPH) is the initial and rate-limiting enzyme in serotonin biosynthesis. The enzyme activity is dependent on molecular oxygen, a tetrahydropterin cosubstrate, and ferrous iron. The present study demonstrates that TPH is inhibited by a novel compound, p-Ethynylphenylalanine (pEPA), produced by the Heck reaction of trimethylsilylacetylene with N-tertbutyloxycarbonyl-4-iodo-L-phenylalanine methyl ester. pEPA is a more potent and specific inhibitor of TPH than p-chlorophenylalanine (pCPA). In the present study, pEPA was demonstrated to inhibit competitively and reversibly TPH in vitro (Ki = 32.6 +/- 6.2 microM vs. tryptophan). pEPA displayed little inhibitory activity toward tyrosine hydroxylase (EC 1.14.16.2), the initial and rate-limiting enzyme for catecholamine biosynthesis, and no inhibition of phenylalanine hydroxylase or tyrosinase. In addition, pEPA was a poor ligand for the serotonin transporter and several serotonin receptors. Administration of pEPA (30 mg/kg) to rats produced a 95 +/- 5% decrease in TPH activity in brain homogenates and a concomitant decrease in serotonin and 5-hydroxyindole-3-acetic acid levels (85%) at 24 h after injection. In contrast, pCPA produced a similar effect (87 +/- 5% decrease in TPH activity) only at 10 times the concentration (300 mg/kg). These results suggest that pEPA is a selective, reversible, and potent inhibitor of TPH both in vitro and in vivo. The potential for pEPA to inhibit selectively and reversibly the biosynthesis of serotonin may contribute to the characterization of the role of serotonin in behavioral and physiological activities.
Short- and long-term effects of p-Ethynylphenylalanine on brain serotonin levels
Neurochem Res 2002 Apr;27(4):269-75.PMID:11958527DOI:10.1023/a:1014998926763.
Changes in tissue and extracellular serotonin (5-HT) in raphe dorsalis, raphe medialis and in their main projections areas (hippocampus, striatum and frontal cortex) were investigated at short and long-term times after single injection (5 mg/kg ip) of a novel tryptophan hydroxylase inhibitor, p-Ethynylphenylalanine (p-EPA). The 5-HT tissue concentration decreased significantly in raphe nuclei, 30 min post-injection and for 4 days, whereas it decreased from 24 hours post-injection in the 5-HT projections. Normal 5-HT levels reappeared after 12 days post-injection in all areas. Moreover, in the projection areas, the extracellular 5-HT levels decreased rapidly, 90, 40 and 30 min after p-EPA injection, in hippocampus, striatum and frontal cortex, respectively. Decreased accumulation of 5-hydroxytryptophan (5-HTP) under NSD-101 perfusion in the serotoninergic projections after p-EPA injection, confirmed the direct inhibitory effect of the drug on the tryptophan hydroxylase activity. These results demonstrated that p-EPA is a useful pharmacological tool which powerfully, acutely and irreversibly reduces the 5-HT levels.
Site-specific fatty acid-conjugation to prolong protein half-life in vivo
J Control Release 2013 Sep 10;170(2):219-25.PMID:23735573DOI:10.1016/j.jconrel.2013.05.023.
Therapeutic proteins are indispensable in treating numerous human diseases. However, therapeutic proteins often suffer short serum half-life. In order to extend the serum half-life, a natural albumin ligand (a fatty acid) has been conjugated to small therapeutic peptides resulting in a prolonged serum half-life via binding to patients' serum albumin in vivo. However, fatty acid-conjugation has limited applicability due to lack of site-specificity resulting in the heterogeneity of conjugated proteins and a significant loss in pharmaceutical activity. In order to address these issues, we exploited the site-specific fatty acid-conjugation to a permissive site of a protein, using copper-catalyzed alkyne-azide cycloaddition, by linking a fatty acid derivative to p-Ethynylphenylalanine incorporated into a protein using an engineered pair of yeast tRNA/aminoacyl tRNA synthetase. As a proof-of-concept, we show that single palmitic acid conjugated to superfolder green fluorescent protein (sfGFP) in a site-specific manner enhanced a protein's albumin-binding in vitro about 20 times and the serum half-life in vivo 5 times when compared to those of the unmodified sfGFP. Furthermore, the fatty acid conjugation did not cause a significant reduction in the fluorescence of sfGFP. Therefore, these results clearly indicate that the site-specific fatty acid-conjugation is a very promising strategy to prolong protein serum half-life in vivo without compromising its folded structure and activity.
De novo microdeletion of Xp11.3 exclusively encompassing the monoamine oxidase A and B genes in a male infant with episodic hypotonia: a genomics approach to personalized medicine
Eur J Med Genet 2012 May;55(5):349-53.PMID:22365943DOI:10.1016/j.ejmg.2012.01.007.
Monoamine oxidase A and B (MAOA and MAOB) play key roles in deaminating neurotransmitters and various other biogenic amines. Patients deficient in one or both enzymes have distinct metabolic and neurologic profiles. MAOB deficient patients exhibit normal clinical characteristics and behavior, while MAOA deficient patients have borderline intellectual deficiency and impaired impulse control. Patients who lack both MAOA and MAOB have the most extreme laboratory values (urine, blood, and CSF serotonin 4-6 times normal, with elevated O-methylated amine metabolites and reduced deaminated metabolites) in addition to severe intellectual deficiency and behavioral problems. Mice lacking maoa and moab exhibit decreased proliferation of neural stem cells beginning in late gestation and persisting into adulthood. These mice show significantly increased monoamine levels, particularly serotonin, as well as anxiety-like behaviors as adults, suggesting that brain maturation in late embryonic development is adversely affected by elevated serotonin levels. We report the case of a male infant with a de novo Xp11.3 microdeletion exclusively encompassing the MAOA and MAOB genes. This newly recognized X-linked disorder is characterized by severe intellectual disability and unusual episodes of hypotonia, which resemble atonic seizures, but have no EEG correlate. A customized low dietary amine diet was implemented in an attempt to prevent the cardiovascular complications that can result from the excessive intake of these compounds. This is the second report of this deletion and the first attempt to maintain the patient's cardiovascular health through dietary manipulation. Even though a diet low in tyramine, phenylethylamine, and dopa/dopamine is necessary for long-term management, it will not rescue the abnormal monoamine profile seen in combined MAOA and MAOB deficiency. Our patient displays markedly elevated levels of serotonin in blood, serum, urine, and CSF while on this diet. Serotonin biosynthesis inhibitors like para-chlorophenylalanine and p-Ethynylphenylalanine may be needed to lower serotonin levels in patients with absent monoamine oxidase enzymes.
Frequency Changes in Terminal Alkynes Provide Strong, Sensitive, and Solvatochromic Raman Probes of Biochemical Environments
J Phys Chem B 2023 Jan 12;127(1):85-94.PMID:PMC9841980DOI:10.1021/acs.jpcb.2c06176.
The C≡C stretching frequencies of terminal alkynes appear in the "clear" window of vibrational spectra, so they are attractive and increasingly popular as site-specific probes in complicated biological systems like proteins, cells, and tissues. In this work, we collected infrared (IR) absorption and Raman scattering spectra of model compounds, artificial amino acids, and model proteins that contain terminal alkyne groups, and we used our results to draw conclusions about the signal strength and sensitivity to the local environment of both aliphatic and aromatic terminal alkyne C≡C stretching bands. While the IR bands of alkynyl model compounds displayed surprisingly broad solvatochromism, their absorptions were weak enough that alkynes can be ruled out as effective IR probes. The same solvatochromism was observed in model compounds' Raman spectra, and comparisons to published empirical solvent scales (including a linear regression against four meta-aggregated solvent parameters) suggested that the alkyne C≡C stretching frequency mainly reports on local electronic interactions (i.e., short-range electron donor-acceptor interactions) with solvent molecules and neighboring functional groups. The strong solvatochromism observed here for alkyne stretching bands introduces an important consideration for Raman imaging studies based on these signals. Raman signals for alkynes (especially those that are π-conjugated) can be exceptionally strong and should permit alkynyl Raman signals to function as probes at very low concentrations, as compared to other widely used vibrational probe groups like azides and nitriles. We incorporated homopropargyl glycine into a transmembrane helical peptide via peptide synthesis, and we installed p-Ethynylphenylalanine into the interior of the Escherichia coli fatty acid acyl carrier protein using a genetic code expansion technique. The Raman spectra from each of these test systems indicate that alkynyl C≡C bands can act as effective and unique probes of their local biomolecular environments. We provide guidance for the best possible future uses of alkynes as solvatochromic Raman probes, and while empirical explanations of the alkyne solvatochromism are offered, open questions about its physical basis are enunciated.