CN111072681A - Fluorescent probe for GABA receptor on surface of target cell membrane as well as preparation method and application of fluorescent probe - Google Patents
Fluorescent probe for GABA receptor on surface of target cell membrane as well as preparation method and application of fluorescent probe Download PDFInfo
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Abstract
The invention belongs to the field of preparation of fluorescent probes for GABA receptors on cell membrane surfaces, relates to application of coumarin derivatives as fluorescent probes for GABA receptors on cell membrane surfaces, and particularly relates to a fluorescent probe for GABA receptors on cell membrane surfaces as well as a preparation method and application of the fluorescent probe. The structural formula of the fluorescent probe is shown as
. The probe of the invention has simple synthesis, high yield, good specificity and high signal-to-noise ratio, can quickly target the receptor of the corresponding cell membrane, and can target the cell membrane for a long time. In confocal imaging experiments, the probe can well target GABA receptors on the surface of cell membranes.
Description
Technical Field
The invention belongs to the field of preparation of fluorescent probes for GABA receptors on cell membrane surfaces, relates to application of coumarin derivatives as fluorescent probes for GABA receptors on cell membrane surfaces, and particularly relates to a fluorescent probe for GABA receptors on cell membrane surfaces as well as a preparation method and application of the fluorescent probe.
Background
The epidermal cell membrane is mainly a semipermeable membrane composed of phospholipids, and can be roughly divided into glycerophospholipids, lipid rafts and transmembrane ion channels according to the composition structure, and the glycerophospholipids, the lipid rafts and the transmembrane ion channels wrap cells, so that the whole cell is in a relatively stable state by executing physiological functions of selective absorption, exchange, discharge and the like, and further normal life activities are maintained. Therefore, it is necessary to develop a fluorescent probe targeting cell membranes and to track its dynamic changes. Some probes targeting cell membranes are reported, such as Dio, Dil, DiD, DiR, and the like, and these molecules all contain a longer alkane chain structure to increase the hydrophobicity of the molecules themselves, so that the molecules can be embedded into the phospholipid bilayer membrane during imaging of the cell membrane, but at the same time, strong background signal interference is inevitably generated, the signal-to-noise ratio is further reduced, the imaging of the cell membrane is not facilitated, and in addition, due to the non-specificity of the targeted cell membrane, the molecules can enter the cell after imaging for a period of time, so that the probes are not suitable for imaging the cell membrane in real time for a long time. In addition, some cell membrane probes which are not commercially applied are reported, and the probes are usually coated with a PEG long-chain structure or modify an antibody targeting a certain receptor of a cell membrane, so that the design process is complicated, the synthesis steps are more, and the reasonable development and use of the probes are not facilitated. Therefore, it is very interesting to develop a probe having specificity, simple synthesis and long-term targeting membrane function.
Barbituric acid is a basic unit constituting sedative-hypnotic drugs, and exerts corresponding pharmacological effects mainly by binding to the barbituric binding site on GABA receptors on the cell membrane surface. In the application, the inventor designs and synthesizes a fluorescent small molecule probe 8- (diethylenelamino) -2-thioxo-2, 3-dihydo-4H-chromeno [2,3-d ] pyrimidin-4-one (1) which can be targeted for a long time and has high signal-to-noise ratio and no washing by taking a coumarin basic structure as a mother nucleus and combining with thiobarbituric acid. The coumarin nucleus structure has good fluorescence characteristics, and the barbituric acid derivative can be combined with barbituric sites on specific GABA receptors on membranes, so that the purpose of cell membrane imaging experiments can be achieved.
Disclosure of Invention
The invention provides a fluorescence probe of a GABA receptor on the surface of a target cell membrane as well as a preparation method and application thereof. The probe has weaker fluorescence in a solution with larger polarity, and the polarity is weakened after the probe is combined with a corresponding receptor on a cell membrane, so that the fluorescence intensity of the system is increased, and the aim of specific targeting can be fulfilled.
The technical scheme of the invention is realized as follows:
a fluorescence probe of GABA receptor on the surface of target cell membrane has a structural formula
。
The preparation method of the fluorescence probe of the GABA receptor on the surface of the target cell membrane comprises the following steps: adding 4- (diethylamino) salicylaldehyde and 4, 6-dihydroxy-2-mercaptopyrimidine into a flask, then adding concentrated sulfuric acid, uniformly mixing, carrying out condensation reflux for 6-8 h under the condition of oil bath at 90-95 ℃, cooling to room temperature, adding ice blocks for dilution, dropwise adding a perchloric acid solution under the condition of stirring, then carrying out suction filtration to obtain a crude product, washing the crude product with absolute ethyl alcohol, and purifying to obtain a solid product, namely the GABA receptor fluorescent probe.
The molar ratio of the 4- (diethylamino) salicylaldehyde to the 4, 6-dihydroxy-2-mercaptopyrimidine is 1: (1-1.02) concentrated sulfuric acid was added in an amount of 0.4mL per 0.01mol of 4- (diethylamino) salicylaldehyde.
The fluorescent probe is applied to the target recognition of GABA receptors on cell membranes.
The method comprises the following steps: dissolving the fluorescent probe in DMSO to prepare a probe stock solution, then adding the probe stock solution into PBS buffer solution of a sample to be detected, uniformly mixing, and carrying out fluorescence spectrum test under the excitation wavelength of 480 nm.
The concentration of the probe stock solution is 2 mM, the concentration of the PBS buffer solution of the sample to be detected is 10 mM, and the pH value is 7.4.
The volume ratio of the probe stock solution to the PBS buffer solution of the sample to be detected is 1: 200.
The invention has the following beneficial effects:
(1) the invention takes coumarin as a basic structure as a fluorescent group, has the advantages of good photostability, high quantum yield, easy modification and high biocompatibility and the like, and is connected with thiobarbituric acid as a functional group targeting GABA receptors on the basis so as to realize the targeting function of corresponding receptors on cell membranes; when a cell feasibility experiment is carried out, the probe can well target a cell membrane; and later, a reverse validation experiment is carried out through an antagonist of the corresponding receptor, and the specificity of the receptor is proved to target GABA receptor. The probe of the invention has simple synthesis, high yield, good specificity and high signal-to-noise ratio, can quickly target the receptor of the corresponding cell membrane, and can target the cell membrane for a long time. In confocal imaging experiments, the probe can well target GABA receptors on the surface of cell membranes.
(2) The probe of the invention has simple synthesis, high yield, good specificity and high sensitivity, and can quickly target GABA receptors on the surface of cell membranes. Compared with commercial cell membrane dyes, the dye has the advantages of long-time targeting, no washing, high signal-to-noise ratio and the like. The method provides a new idea and method for developing the cell membrane targeted small-molecule fluorescent probe.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the drawings without creative efforts.
Fig. 1 is a graph of fluorescence excitation and emission spectra of a 5 μ M probe in a PBS buffered (10 mM, pH = 7.4) system.
FIG. 2 is a bar graph of the cell viability of the probes at different concentrations after 24h incubation with cells in DMEM medium containing serum.
FIG. 3 is a fluorescent confocal cell membrane co-localization spectrogram after co-incubation and elution of a 5 μ M probe and a commercial cell membrane dye Dil in a colorless DMEM medium.
FIG. 4 is a bar graph of fluorescence intensity changes under 480nm excitation after mixing of 5 μ M probes with different types of surfactants in a wash-free validation experiment in a PBS buffered (10 mM, pH = 7.4) system.
FIG. 5 is a plot of signal to noise ratio before and after elution of cells under 480nm excitation when a 5 μ M probe was incubated with the cells in colorless DMEM medium with a scale size of 25 μ M.
FIG. 6 is a picture of confocal imaging performed under different time conditions when a 5 μ M probe was incubated with cells in colorless DMEM medium, with a scale size of 25 μ M.
FIG. 7 is a graph of confocal imaging results under 480nm excitation, eluted after incubation of 5 μ M commercial cell membrane dye Dil with cells for different times in colorless DMEM medium, with the scale size of 25 μ M.
FIG. 8 is a result of confocal imaging performed after the GABA receptor antagonist tetrandrine is added to the colorless DMEM medium and incubated with the cells, and then the 5 μ M probe is added to the cells and incubated with the cells, wherein the size of the scale is 25 μ M.
FIG. 9 shows the NMR spectrum of a fluorescent probe.
FIG. 10 is a nuclear magnetic resonance carbon spectrum of a fluorescent probe.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments of the present invention, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without inventive effort based on the embodiments of the present invention, are within the scope of the present invention.
Example 1
The preparation process of the fluorescent probe for the GABA receptor on the surface of the target cell membrane comprises the following steps:
the preparation method comprises the following steps:
accurately weighing 0.0025 mol of each of 4- (diethylamino) salicylaldehyde and 4, 6-dihydroxy-2-mercaptopyrimidine, adding the weighed materials into a dry round-bottom flask, adding 10 mL of concentrated sulfuric acid, uniformly mixing, carrying out condensation reflux for 6 hours at 90 ℃ under the condition of oil bath, cooling to room temperature, adding a proper amount of ice blocks for dilution, dropwise adding a perchloric acid solution under the stirring condition, carrying out suction filtration to obtain a crude product, namely a reddish brown solid, and washing the obtained solid with absolute ethyl alcohol to purify the crude product. The final product mass was 0.5721g, giving a product yield of 76%. The NMR spectrum of the product probe is shown in FIG. 9; the NMR spectrum is shown in FIG. 10.
Example 2
The preparation process of the fluorescent probe for the GABA receptor on the surface of the target cell membrane comprises the following steps:
the preparation method comprises the following steps:
accurately weighing 0.0025 mol of 4- (diethylamino) salicylaldehyde and 0.00266 mol of 4, 6-dihydroxy-2-mercaptopyrimidine, adding the 4- (diethylamino) salicylaldehyde and the 0.00266 mol of 4, 6-dihydroxy-2-mercaptopyrimidine into a dry round-bottom flask, then adding 10 mL of concentrated sulfuric acid, uniformly mixing, condensing and refluxing for 6 hours under the condition of 90 ℃ oil bath, cooling to room temperature, adding a proper amount of ice blocks for dilution, dropwise adding a perchloric acid solution under the stirring condition, carrying out suction filtration to obtain a crude product, namely a reddish brown solid, and washing the obtained solid with absolute ethyl alcohol to purify. The final product mass was 0.6022g, giving a 79.8% yield.
Examples of the effects of the invention
1. Fluorescence profile of probe in PBS buffered (10 mM, pH = 7.4) system.
Preparing a PBS (10 mM) buffer solution at pH = 7.4; the probe prepared in example 1 was weighed, dissolved in DMSO, and a 2 mM probe stock solution was prepared accurately. After 2mL of PBS buffer was added to the cuvette, 5. mu.L of a 2 mM probe stock was added to perform fluorescence excitation and emission spectroscopy. As shown in FIG. 1, the probe had an excitation wavelength of 480nm and an emission wavelength of 520 nm.
2. Cell viability following co-incubation of the probe with the cells.
Firstly, preparing HepG-2 cell suspension, then adding cell suspension with the volume of 100 mu L and the density of 2000/hole into a 96-hole plate, putting the cell suspension into an incubator to be cultured to an adherent state, adding probe solutions (1, 2, 5,8, 10 and20 mu M) with different concentrations, incubating the cell suspension and the cells together for 24h, then using CCK-8 to determine cytotoxicity, replacing the culture medium in each hole with fresh culture medium, adding 10 mu L CCK-8 into each hole, incubating for 2 h at 37 ℃, using a microplate reader (TECAN SPARKMagellan) to detect the light absorption value of each hole at 450nm, and finally using the formula of cell survival rate (%) [ (As-Ab)/(Ac-Ab) ] × 100% (As: experimental hole; Ac: control hole; Ab: blank hole) to calculate the cell survival rate and further evaluate the toxicity of the probe, the results are shown in fig. 2, and it can be found from the related results that the cell survival rate can still be ensured to be more than 80% when the concentration of the probe molecule is higher, which indicates that the toxicity of the molecule to the cell is lower, and therefore, the probe molecule can be better applied to the later cell biological imaging experiment.
3. Confocal imaging after co-incubation of probes with cells
And washing the adherent cells with PBS three times, diluting the probe solution to the required concentration by using a colorless DMEM culture medium, adding the diluted probe solution into a dish containing the cells, and performing confocal imaging after co-incubation for a certain time. When cell membrane co-staining experiments are carried out, a commercial cell membrane dye Dil is added to be incubated with cells, then a probe solution is added, after the incubation is finished, the cells are eluted with PBS for three times, and finally colorless DMEM medium is added. When confocal imaging is performed, different excitations are respectively used, different emission bands are collected to avoid mutual interference between the two, the experimental result is shown in fig. 3, the yellow channel of the fluorescent probe can be well overlapped with the commercial dye of the red channel, and the fluorescence intensity diagram of a specific area in the combined graph well proves the point. Therefore, the fluorescent probe molecule can be well positioned on the cell membrane.
4. Wash-free validation experiment of probe molecules
The method comprises the steps of preparing solution with concentration capable of forming critical micelles by using different types of surfactants, then respectively adding probe molecule solution with the same concentration, and detecting the fluorescence intensity value of the probe in the emission wavelength under the same excitation wavelength, wherein the experimental result is shown in figure 4, compared with the fluorescence intensity in PBS buffer solution, the fluorescence intensity of the probe in the surfactant is obviously increased, which shows that after molecules are wrapped into the nonpolar environment in vesicles, the probe has stronger fluorescence, which is consistent with the microenvironment where the probe molecules are located when the cell membranes are targeted, so that the in vitro fluorescence test result verifies the washing-free reason of cell imaging from the side.
5. High signal-to-noise ratio advantage verification experiment
The experiments were divided into two groups: the control group is used for confocal imaging under the condition that the probe molecules are not eluted, and the experimental group is used for imaging after the probe molecules and the cells are incubated for a certain time and are eluted by PBS for three times, and then the signal-to-noise ratio of the probe molecules and the cells is compared. The experimental results are shown in fig. 5, and it can be seen that the non-eluted group still has a higher signal-to-noise ratio compared with the eluted group, which indicates that the probe molecule can still be well applied to biological imaging even under the non-eluted condition.
6. Long-time targeted cell membrane advantage verification experiment
Firstly fixing the imaging concentration of the probe at 5 mu M, then starting timing, and respectively imaging at different time intervals, wherein the experimental result is shown in fig. 6, and the figure shows that the molecule can achieve the purpose of specifically targeting cell membranes in a short time, and the targeted position does not change along with the time extension, so that the molecule is laterally proved to have good specificity in biological imaging, and have the inherent characteristics and related advantages of targeting cell membranes for a long time.
7. Commercial dye incubations for various periods
Firstly, because commercial cell membrane dyes generally have longer alkane chains and positive charges, the purpose of quickly targeting cell membranes can be realized in the early stage of imaging, but with the increase of the co-incubation time with cells, part of the commercial dyes can enter the cells, so that the specificity is poor, the designed probe molecules can achieve the purpose of imaging the cell membranes for a long time, even if the co-incubation time with the cells reaches 3 h, the fluorescent small molecules can still continuously target the cell membranes, and when the commercial dyes Dil are incubated with the cells for 30 min or longer, the cells are eluted by PBS for imaging, and as a result, as shown in FIG. 7, a fluorescent field is found to have fluorescence on the cell membranes, and part of fluorescent signals are generated in cytoplasm, which shows that with the increase of time, the specific targeting ability of the commercial dyes to the cell membranes is weakened, so compared with the commercial dyes, the small molecule probe has the advantage of long-time specific targeting on cell membranes.
8. GABA receptor validation experiment
Firstly, antagonist-tetrandrine which is specifically combined with barbituric acid sites in GABA receptors is selected, the antagonist-tetrandrine is incubated with cells for 20 min, then probes are added, the fluorescence statistical result after imaging is compared with the result after the probe is incubated under normal conditions, the result is shown in figure 8, the fluorescence intensity after the antagonist is added is obviously lower than that of a control group through a corresponding fluorescence field result diagram and the corresponding statistical intensity, which shows that the barbituric acid action sites in the GABA receptors are occupied after the antagonist is added, so that the capacity of combining the probes with the barbituric acid action sites is weakened, the weakening of fluorescence signals is caused, and the binding sites of designed molecules which are potentially targeted to cell membranes are further proved.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (7)
1. A GABA receptor fluorescent probe for targeting the surface of a cell membrane is characterized in that: the structural formula of the fluorescent probe is shown as
。
2. The method for preparing the fluorescent probe for the GABA receptor on the surface of the cell membrane according to claim 1, which comprises the following steps: adding 4- (diethylamino) salicylaldehyde and 4, 6-dihydroxy-2-mercaptopyrimidine into a flask, then adding concentrated sulfuric acid, uniformly mixing, carrying out condensation reflux for 6-8 h under the condition of oil bath at 90-95 ℃, cooling to room temperature, adding ice blocks for dilution, dropwise adding a perchloric acid solution under the condition of stirring, then carrying out suction filtration to obtain a crude product, washing the crude product with absolute ethyl alcohol, and purifying to obtain a solid product, namely the GABA receptor fluorescent probe.
3. The method for preparing a fluorescent probe targeting a GABA receptor on the surface of a cell membrane according to claim 2, which comprises the following steps: the molar ratio of the 4- (diethylamino) salicylaldehyde to the 4, 6-dihydroxy-2-mercaptopyrimidine is 1: (1-1.02) concentrated sulfuric acid was added in an amount of 0.4mL per 0.01mol of 4- (diethylamino) salicylaldehyde.
4. Use of the fluorescent probe of claim 1 for targeted recognition of GABA receptors on cell membranes.
5. The use according to claim 4, characterized by the steps of: dissolving a fluorescent probe in DMSO to prepare a probe stock solution, adding 5 mu L of the solution into 2mL PBS buffer solution, uniformly mixing, and carrying out fluorescence spectrum test at an excitation wavelength of 480 nm.
6. Use according to claim 5, characterized in that: the probe stock solution had a concentration of 2 mM, PBS buffer solution at the time of the test was 10 mM, pH 7.4, and volume 2 mL.
7. Use according to claim 6, characterized in that: the volume ratio of the probe stock solution to the PBS buffer solution was 1: 200.
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| CN113402523A (en) * | 2021-07-13 | 2021-09-17 | 西安交通大学 | Targeted mast cell MrgX2 small-molecule fluorescent probe and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1553909A (en) * | 2000-12-21 | 2004-12-08 | Benzimidazole and pyridylimidazole derivatives as ligands for GABA receptors | |
| CN102532197A (en) * | 2010-12-24 | 2012-07-04 | 中国科学院上海药物研究所 | First glass photoaffinity labeling difunctional probe molecule and preparation method and application thereof |
-
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1553909A (en) * | 2000-12-21 | 2004-12-08 | Benzimidazole and pyridylimidazole derivatives as ligands for GABA receptors | |
| CN102532197A (en) * | 2010-12-24 | 2012-07-04 | 中国科学院上海药物研究所 | First glass photoaffinity labeling difunctional probe molecule and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| KAMMOUN, MYRIAM等: "Reactivity of 3-cyano-N-ethoxycarbonyl-iminocoumarin with hydrazides as N-nucleophiles", 《JOURNAL OF HETEROCYCLIC CHEMISTRY》 * |
| KHALAFI-NEZHAD, ALI等: "Trimethylsilyl iodide as a multifunctional agent in the one-pot synthesis of 9-(1H-indol-3-yl)xanthen-1-(9H)-ones from O-methyl protected salicylaldehydes, indoles and β-dicarbonyl compounds", 《SYNTHESIS》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113402523A (en) * | 2021-07-13 | 2021-09-17 | 西安交通大学 | Targeted mast cell MrgX2 small-molecule fluorescent probe and preparation method and application thereof |
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