D-DOPA
(Synonyms: 3-羟基-D-酪氨酸) 目录号 : GC47174
An enantiomer of L-DOPA
Cas No.:5796-17-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
D-DOPA is an enantiomer of the dopamine precursor L-DOPA . It can be converted to L-DOPA via sequential oxidation and transamination, which are mediated by D-amino acid oxidase (DAAO) and DOPA transaminase, respectively, in rat kidney homogenates.1 It reduces the number of dopaminergic neurons in primary rat embryonic mesencephalic cultures in a concentration-dependent manner.2 Intraventricular administration of D-DOPA (200 µg/animal) increases striatal dopamine levels in rats.3 D-DOPA (20 mg/kg, i.p.) induces contralateral turns in a rat model of Parkinson's disease induced by 6-OHDA .4
1.Wu, M., Zhou, X.-J., Konno, R., et al.D-dopa is unidirectionally converted to L-dopa by D-amino acid oxidase, followed by dopa transaminaseClin. Exp. Pharmacol. Physiol.33(11)1042-1046(2006) 2.Ling, Z.-D., Pieri, S.C., and Carvey, P.M.Comparison of the neurotoxicity of dihydroxyphenylalanine stereoisomers in cultured dopamine neuronsClin. Neuropharmacol.19(4)360-365(1996) 3.Karoum, F., Freed, W.J., Chuang, L.-W., et al.D-dopa and L-dopa similarly elevate brain dopamine and produce turning behavior in ratsBrain Res.440(1)190-194(1988) 4.Moses, J., Siddiqui, A., and Silverman, P.B.Sodium benzoate differentially blocks circling induced by D-and L-dopa in the hemi-parkinsonian ratNeurosci. Lett.218(3)145-148(1996)
| Cas No. | 5796-17-8 | SDF | |
| 别名 | 3-羟基-D-酪氨酸 | ||
| Canonical SMILES | OC1=CC(C[C@@H](N)C(O)=O)=CC=C1O | ||
| 分子式 | C9H11NO4 | 分子量 | 197.2 |
| 溶解度 | 0.1 M HCl: 10 mg/ml | 储存条件 | Store at 2-8°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 | 5.071 mL | 25.355 mL | 50.7099 mL |
| 5 mM | 1.0142 mL | 5.071 mL | 10.142 mL |
| 10 mM | 0.5071 mL | 2.5355 mL | 5.071 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 |
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| % 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。
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D-DOPA Is a Potent, Orally Bioavailable, Allosteric Inhibitor of Glutamate Carboxypeptidase II
Pharmaceutics 2022 Sep 23;14(10):2018.PMID:36297453DOI:10.3390/pharmaceutics14102018.
Glutamate carboxypeptidase-II (GCPII) is a zinc-dependent metalloenzyme implicated in numerous neurological disorders. The pharmacophoric requirements of active-site GCPII inhibitors makes them highly charged, manifesting poor pharmacokinetic (PK) properties. Herein, we describe the discovery and characterization of catechol-based inhibitors including L-DOPA, D-DOPA, and caffeic acid, with sub-micromolar potencies. Of these, D-DOPA emerged as the most promising compound, with good metabolic stability, and excellent PK properties. Orally administered D-DOPA yielded high plasma exposures (AUCplasma = 72.7 nmol·h/mL) and an absolute oral bioavailability of 47.7%. Unfortunately, D-DOPA brain exposures were low with AUCbrain = 2.42 nmol/g and AUCbrain/plasma ratio of 0.03. Given reports of isomeric inversion of D-DOPA to L-DOPA via D-amino acid oxidase (DAAO), we evaluated D-DOPA PK in combination with the DAAO inhibitor sodium benzoate and observed a >200% enhancement in both plasma and brain exposures (AUCplasma = 185 nmol·h/mL; AUCbrain = 5.48 nmol·h/g). Further, we demonstrated GCPII target engagement; orally administered D-DOPA with or without sodium benzoate caused significant inhibition of GCPII activity. Lastly, mode of inhibition studies revealed D-DOPA to be a noncompetitive, allosteric inhibitor of GCPII. To our knowledge, this is the first report of D-DOPA as a distinct scaffold for GCPII inhibition, laying the groundwork for future optimization to obtain clinically viable candidates.
L-DOPA, a treatment for Parkinson's disease, and its enantiomer D-DOPA inhibit severe fever with thrombocytopenia syndrome virus infection in vitro
J Infect Chemother 2022 Mar;28(3):373-376.PMID:34802888DOI:10.1016/j.jiac.2021.11.005.
Severe fever with thrombocytopenia syndrome (SFTS) is a hemorrhagic fever. Patients mainly develop fever, thrombocytopenia, and leukopenia. A high case fatality rate of 16.2-47% has been reported. Vaccines and antivirals that are effective against SFTS virus (SFTSV) are not yet available in clinical practice. We previously showed that o-dihydroxybenzene is the important chemical core structure for anti-SFTSV activity. In this study, we evaluated the anti-SFTSV efficacy of 3-Hydroxy-L-tyrosine (L-DOPA), a treatment for Parkinson's disease and its enantiomer, 3-hydroxy-D-tyrosine (D-DOPA), both of which have an o-dihydroxybenzene backbone. SFTSV was preincubated with L- or D-DOPA and then inhibition of viral infection as well as viral attachment to host cells were evaluated by viral quantification. Both L- and D-DOPA inhibited SFTSV infection in a dose-dependent manner, mainly by blocking viral attachment to host cells. The half-maximal inhibitory concentration (IC50) of L-DOPA was 4.46-5.09 μM. IC50 of D-DOPA was 4.23-6.72 μM. IC50 of L-DOPA is very close to its maximum blood concentration after oral administration as a therapy for Parkinson's disease. D-DOPA, which IC50 was almost the same as that of L-DOPA, might not cause side effect. Thus, our present study demonstrated that L- and D-DOPA are potentially useful candidates for anti-SFTSV drugs.
D-DOPA and L-dopa similarly elevate brain dopamine and produce turning behavior in rats
Brain Res 1988 Feb 2;440(1):190-4.PMID:3129126DOI:10.1016/0006-8993(88)91176-6.
In the intact rat, intragastric administration of D-dihydroxyphenylalanine (D-DOPA) together with carbidopa (alpha-methyldopa hydrazine, a peripheral dopadecarboxylase inhibitor) increased striatal dopamine concentration to the same extent as a similar treatment with L-DOPA plus carbidopa. In rats with unilateral 6-hydroxydopamine-induced lesions of their substantia nigra, both stereoisomers of DOPA produced significant increases in dopamine and its metabolites in the intact striata. Although dopamine concentrations in the lesioned striata did not change, a significant increase in dopamine metabolites was observed, indicating some extraneuronal formation of dopamine. These results suggest that D-DOPA can be converted to dopamine in the normal striatum as well as in the striatum devoid of dopamine nerve terminals. D- and L-DOPA produced turning behavior in unilaterally lesioned rats with a similar efficacy. The onset of turning after D-DOPA was delayed compared with L-DOPA. Turning behavior elicited by these amino acids was attributed to stimulation of supersensitive dopamine receptors in the lesioned striata by the extraneuronally formed dopamine. Preliminary results suggest that D-DOPA is converted to dopamine via transamination and/or D-amino acid oxidation to 3,4-dihydroxyphenylpyruvic acid which upon further transamination gives rise to L-DOPA and hence dopamine. The relatively fast and slow onset of stimulation of dopamine receptors L-DOPA and D-DOPA respectively suggests that the use of the racemic mixture of DOPA combined with a peripheral dopadecarboxylase inhibitor may prove useful in the treatment of parkinsonism.
Study of tyrosine and dopa enantiomers as tyrosinase substrates initiating l- and d-melanogenesis pathways
Biotechnol Appl Biochem 2021 Aug;68(4):823-831.PMID:32776353DOI:10.1002/bab.1998.
Tyrosinase starts melanogenesis and determines its course, catalyzing the oxidation by molecular oxygen of tyrosine to dopa, and that of dopa to dopaquinone. Then, nonenzymatic coupling reactions lead to dopachrome, which evolves toward melanin. Recently, it has been reported that d-tyrosine acts as tyrosinase inhibitor and depigmenting agent. The action of tyrosinase on the enantiomers of tyrosine (l-tyrosine and d-tyrosine) and dopa (l-dopa and D-DOPA) was studied for the first time focusing on quantitative transient phase kinetics. Post-steady-state transient phase studies revealed that l-dopachrome is formed more rapidly than d-dopachrome. This is due to the lower values of Michaelis constants for l-enantiomers than for d-enantiomers, although the maximum rates are equal for both enantiomers. A deeper analysis of the inter-steady-state transient phase of monophenols demonstrated that the enantiomer d-tyrosine causes a longer lag period and a lower steady-state rate, than l-tyrosine at the same concentration. Therefore, d-melanogenesis from d-tyrosine occurs more slowly than does l-melanogenesis from l-tyrosine, which suggests the apparent inhibition of melanin biosynthesis by d-tyrosine. As conclusion, d-tyrosine acts as a real substrate of tyrosinase, with low catalytic efficiency and, therefore, delays the formation of d-melanin.
D-DOPA is unidirectionally converted to L-dopa by D-amino acid oxidase, followed by dopa transaminase
Clin Exp Pharmacol Physiol 2006 Nov;33(11):1042-6.PMID:17042912DOI:10.1111/j.1440-1681.2006.04484.x.
1. Many studies have shown that administration of d-3, 4-dihydroxyphenylalanine (D-DOPA) produces contralateral rotation in hemi-parkinsonian animals comparable to L-dopa, with less potency and slower onset. It was postulated that D-DOPA was converted to L-dopa to produce these effects. 2. To investigate the postulated chiral inversion of D-DOPA to L-dopa and the related mechanism, an enantiomeric separation method for D- and L-dopa using HPLC was first established. Then, rat kidney homogenates containing D-DOPA or L-dopa were incubated and subjected to HPLC to detect traces of respective enantiomer generation. The mechanism of the chiral inversion of D-DOPA was explored by direct measurement of the production of L-dopa in kidney homogenates. D-DOPA incubations containing different concentrations of an inhibitor of D-amino acid oxidase (DAAO) and an inhibitor of dopa transaminase were measured for L-dopa generation using HPLC. The role of DAAO in the chiral inversion of D-DOPA to L-dopa was further investigated by using purified DAAO and mutant ddY/DAAO- mouse kidney lacking DAAO activity. 3. In rat kidney homogenate, D-DOPA was, indeed, converted to L-dopa, whereas L-dopa was not converted to D-DOPA. Sodium benzoate, a selective inhibitor of DAAO, blocked L-dopa generation in a concentration-dependant manner. In contrast with kidney homogenates of wild-type ddY/DAAO+ mice, those of mutant ddY/DAAO- mice lacking DAAO activity did not convert D-DOPA to L-dopa unless exogenous DAAO protein was added. Conversely, when carbidopa, an inhibitor of dopa transaminase, was added to the homogenates, significant inhibition of L-dopa production was noted. 4. These results prove the proposal that D-DOPA undergoes unidirectional chiral inversion and further suggest that D-DOPA is first oxidatively deaminated by DAAO to its alpha-keto acid and then transaminated by dopa transaminase to L-dopa.