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Fluorescent probe for analyzing, testing and screening galactokinase inhibitor

The technology of galactokinase and fluorescent probe is applied in the field of biological analysis and detection, which can solve the problems of interference of test results, complicated preparation and purification of galactose kinase, and the effect of simplifying the screening process.

Active Publication Date: 2017-03-08
上海捷虹新材料科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This screening method involves tedious preparation and purification of galactokinase, and the interaction between the inhibitor itself and ATP will inevitably interfere with the test results

Method used

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  • Fluorescent probe for analyzing, testing and screening galactokinase inhibitor
  • Fluorescent probe for analyzing, testing and screening galactokinase inhibitor
  • Fluorescent probe for analyzing, testing and screening galactokinase inhibitor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0058] Compound (I-1) is synthesized in the following manner

[0059]

[0060] (1) Synthesis of compound 1a:

[0061] 1) Add cy3 (246.5mg) to dry DMF (dimethylformamide) (10ml) at room temperature, cool to 0°C, replace the air in the flask with nitrogen, and add TBTU(O- Benzotriazole-N,N,N',N'-tetramethyluronium tetrafluoroborate) (176.5 mg).

[0062] 2) Stir the reaction solution at room temperature for 15 minutes under the protection of nitrogen, then sequentially add 6-amino-6-deoxy-1,2,3,4-di-oxo-isopropyl-α-D-galactose (142.62mg ) and triethylamine (TEA) (151.8 mg), the reaction solution was reacted at room temperature for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation, and the organic phase was extracted with dichloromethane solution to obtain a crude product. The reaction product was simply purified by silica gel column chromatography (dichloromethane:methanol=45:1) to obtain 304.7 mg of a blue solid product .

[0063] Y...

Embodiment 2

[0070] Compound (I-2) is synthesized in the following manner

[0071]

[0072] (1) Synthesis of compound 2a:

[0073] 1) Add cy3 (200.5 mg) and 1,2:3,4-oxo-isopropylidene-α-D-galactofuranose (106.0 mg) to a dry DCM solution (dichloromethane) at room temperature (10 ml), the air in the flask was replaced with nitrogen.

[0074] 2) An equivalent amount of 4-dimethylaminopyridine (DMAP) was added to the reaction solution and then stirred at room temperature for 1 hour under nitrogen protection. N,N'-dicyclohexylcarbodiimide (N,N'-dicyclohexylcarbodiimide) (100.8 mg) was added, and the reaction solution was reacted at room temperature for 12 hours. After the reaction was completed, the solvent was removed by rotary evaporation, and the organic phase was extracted with dichloromethane solution to obtain a crude product. The reaction product was simply purified by silica gel column chromatography (dichloromethane:methanol=45:1) to obtain 133.1 mg of a red solid product.

[007...

Embodiment 3

[0081] Compound (I-3) is synthesized in the following manner

[0082]

[0083] (1) Synthesis of compound 3a:

[0084]Referring to the synthesis method of compound 1a, the starting material was changed to cy5 to finally obtain compound 3a.

[0085] Yield: 80.3%

[0086] 1 H NMR (600MHz, CDCl 3 )δ8.04(d, J=10.8Hz, 2H), 7.36(d, J=5.5Hz, 4H), 7.22(t, J=7.1Hz, 2H), 7.10(dd, J=15.2, 7.8Hz, 2H), 6.70(s, 1H), 6.20(t, J=12.9Hz, 2H), 5.50(d, J=4.4Hz, 1H), 4.59(d, J=7.7Hz, 1H), 4.30(s, 1H), 4.22(d, J=7.7Hz, 1H), 4.00(s, 2H), 3.93(d, J=5.8Hz, 1H), 3.64(d, J=14.6Hz, 4H), 3.28(d, J=9.3Hz, 1H), 2.25(s, 2H), 1.81(s, 2H), 1.72(d, J=12.3Hz, 14H), 1.51(d, J=15.1Hz, 2H), 1.49(s, 3H), 1.45(s,3H), 1.34(s,3H), 1.31(s,3H).

[0087] (2) Synthesis of Compound I-3:

[0088] Referring to the synthesis method of I-1, compound I-3 was finally obtained.

[0089] Yield: 68.1% (see Figure-2 for its excitation and emission spectra)

[0090] 1 H NMR (600MHz, MeOD) δ8.26 (t, J = 12.9Hz, 2H), 7.51 (...

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PUM

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Abstract

The invention discloses a fluorescent probe for analyzing, testing and screening a galactokinase inhibitor. The structure of the fluorescent probe is shown in the formula (I) in the specification, wherein X is O or NH, and R2 is selected from compounds as shown in the specification. The fluorescent probe can simplify the conventional screening process of the galactokinase inhibitor and is directly used in any cell system expressing galactokinase without use of purified and refined galactokinase protein; with the application of the fluorescent probe, purposes of analyzing, testing and screening the galactosidase inhibitor can be achieved conveniently and rapidly, and an effective means and a useful tool are provided for discovery and development of lead compounds and effective drugs capable of preventing and treating the galactosemia disease.

Description

technical field [0001] The invention belongs to the field of biological analysis and detection, and in particular relates to a fluorescent probe for analysis, detection and screening of galactokinase inhibitors, a preparation method and an application. [0002] technical background [0003] Galactosemia is a disease in which galactose in the blood and urine increases. The disease that occurs frequently in newborns or infants is due to the genetic deficiency of galactose-l-phosphate uridyltransferase (GALT), which leads to galactose The first step metabolite of lactose, galactose-l-phosphate (Gal-1-P), is caused by a large accumulation of tissues and cells in the patient's body. The main symptoms of galactosemia are nutritional disorders, cataracts, jaundice, diarrhea, sepsis, mental retardation and hepatosplenomegaly, neonatal death, etc. The clinical treatment of galactosemia mainly includes intravenous glucose supplementation therapy, fresh plasma infusion, electrolyte sup...

Claims

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Application Information

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IPC IPC(8): C07H13/04C07H1/00C09K11/06G01N21/64
CPCC07H1/00C07H13/04C09K11/06C09K2211/1088G01N21/6486Y02P20/55
Inventor 高清志刘胜男黄振华
Owner 上海捷虹新材料科技有限公司
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