WO2020054462A1 - 生体膜ホスホイノシタイドの分離方法 - Google Patents
生体膜ホスホイノシタイドの分離方法 Download PDFInfo
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- WO2020054462A1 WO2020054462A1 PCT/JP2019/034134 JP2019034134W WO2020054462A1 WO 2020054462 A1 WO2020054462 A1 WO 2020054462A1 JP 2019034134 W JP2019034134 W JP 2019034134W WO 2020054462 A1 WO2020054462 A1 WO 2020054462A1
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- BQVXNQROYRPCLU-UHFFFAOYSA-N C(C(C1)C2)C1C2C1C=CC=C1 Chemical compound C(C(C1)C2)C1C2C1C=CC=C1 BQVXNQROYRPCLU-UHFFFAOYSA-N 0.000 description 1
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
- B01J20/3204—Inorganic carriers, supports or substrates
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D15/00—Separating processes involving the treatment of liquids with solid sorbents; Apparatus therefor
- B01D15/08—Selective adsorption, e.g. chromatography
- B01D15/26—Selective adsorption, e.g. chromatography characterised by the separation mechanism
- B01D15/40—Selective adsorption, e.g. chromatography characterised by the separation mechanism using supercritical fluid as mobile phase or eluent
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/24—Naturally occurring macromolecular compounds, e.g. humic acids or their derivatives
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
- B01J20/282—Porous sorbents
- B01J20/285—Porous sorbents based on polymers
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/16—Injection
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/72—Mass spectrometers
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
- G01N2030/8813—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials
Definitions
- the present invention relates to a method for separating a phosphomembrane phosphoinositide, which is a phospholipid in which the 3,4,5-hydroxyl group of the inositol ring of phosphatidylinositol is phosphorylated.
- PIPs phosphoinositides
- PIPs include PI (3) P, PI (4) P, PI (5) P, There are seven types, PI (3,4) P 2 , PI (3,5) P 2 , PI (4,5) P 2 , and PI (3,4,5) P 3 .
- PI (3) P, PI (4) P, PI (5) P, PI (3,4) P 2 , PI (3,5) P 2 , PI (4, 5) for having three are each isomer same mass of P 2, in order to quantify the seven PIPs individually, need to separate the isomers by chromatography is there.
- PI (3) P, PI (4) P, PI (5) P is regarded as PIP 1 and PI (3,4) P 2 , PI (3) , 5) P 2, PI (4,5) P 2 as PIP 2, quantification of each difference in the type of diacylglycerol (DG) is made. Therefore, quantification for each isomer cannot be performed.
- An object of the present invention is to provide a separation method capable of separating PIPs isomers without deacylating PIPs.
- R 1 in FIG. 4 is a spacer consisting of an alkyl group and a polar group.
- a sample containing a plurality of types of PIPs is injected into an analytical flow path of a supercritical fluid chromatograph having a separation column filled with a separation medium containing ⁇ -cyclodextrin. And a separating step of separating the plurality of types of PIPs from each other by supercritical fluid chromatography.
- the separation method of the present invention is suitable for separating a sample containing a plurality of isomers of PIPs.
- a derivatization step of derivatizing phosphate groups of the plurality of types of PIPs contained in a sample with trimethylsilyl-diazomethane is provided.
- the plurality of PIPs separated by the separation column is derivatized. It is preferable to include a detection step of detecting each type of PIPs by a mass spectrometer. Then, each PIPs containing isomers separated through a separation column filled with a separation medium containing ⁇ -cyclodextrin can be quantitatively analyzed by a mass spectrometer. Individual quantification of different types of PIPs can be realized.
- an aqueous methanolic formate solution can be used as a modifier.
- the method for separating PIPs comprises: injecting a sample containing a plurality of types of PIPs into an analysis channel of a supercritical fluid chromatograph having a separation column filled with a separation medium containing ⁇ -cyclodextrin; Since the method includes a separation step of separating the plurality of types of PIPs from each other by supercritical fluid chromatography, it is possible to separate isomers of PIPs without performing deacylation.
- FIG. 3 is a flow path configuration diagram showing a configuration of a supercritical fluid chromatograph. 4 is a flowchart illustrating an embodiment of a method for separating PIPs.
- FIG. 3 is a diagram for explaining the interaction between PIPs and a separation medium containing ⁇ -cyclodextrin. It is an example of a chromatogram based on the signal of the mass spectrometer obtained by the separation method of the same example.
- the separation method of this example is performed using a supercritical fluid chromatograph (hereinafter, SFC).
- SFC supercritical fluid chromatograph
- the SFC used in this embodiment includes liquid feed pumps 4 and 6 for transmitting carbon dioxide and a modifier in the analysis flow path 2, and a mixing of carbon dioxide and the modifier.
- a sample injecting section 8 for injecting a sample into the analysis channel 2 through which the fluid flows, a separation column 10 for separating the sample injected by the sample injecting section 8, and at least carbon dioxide flowing through the separation column 10
- a back pressure controller (BPR) 12 for controlling the pressure in the analysis flow path 2 to a predetermined pressure so as to be in a critical state, a pump 15 for feeding makeup for highly sensitive detection, and a downstream side of the BPR 12 And a mass spectrometer (MS) 14 provided.
- BPR back pressure controller
- the separation column 10 is housed in a column oven, and is controlled to a fixed temperature.
- the separation column 10 is packed with a separation medium in which a cyclodextrin capable of including an organic substance is bound to a silica carrier.
- a separation medium in which a cyclodextrin capable of including an organic substance is bound to a silica carrier.
- ULTRON AF-HILIC-CD manufactured by Shinwa Kako Co., Ltd. can be used.
- a phosphate group of the PIPs in the sample is derivatized, and each PIP is made detectable by the MS14.
- the derivatization treatment can be performed, for example, by the following procedures (1) to (5).
- a 2 M trimethylsilyl-diazomethanehexane solution is added to a sample solution containing PIPs.
- the sample solution to which the 2M trimethylsilyl-diazomethanehexane solution has been added is left at room temperature for a certain period of time (for example, 10 minutes) to perform a derivatization reaction.
- Glacial acetic acid is added to the sample solution under a nitrogen atmosphere to stop the derivatization reaction.
- methanol containing formic acid or ammonium formate for example, 0.1% formic acid methanol
- Step S1 the sample is injected by the sample injection unit 8 into the SFC analysis channel. 2 (Step S2), and the isomers of PIPs are separated by a separation column 10 packed with a separation medium in which cyclodextrin is bound to a silica carrier (Step S3). Further, the PIPs separated by the separation column 10 are sequentially introduced into the MS 14 and detected (step S4).
- ULTON AF-HILIC-CD inner diameter 4.6 mm, length 250 mm
- the set temperature of the separation column 10 was 4 ° C.
- the flow rate of the mobile phase was 3 mL / min
- the flow rate of the make-up was 0.1 mL / min
- the set pressure of BPR12 was 10 MPa.
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- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
Abstract
Description
(1)PIPsを含む試料溶液に2M トリメチルシリル-ジアゾメタンヘキサン溶液を添加する。
(2)2M トリメチルシリル-ジアゾメタンヘキサン溶液の添加された試料溶液を室温で一定時間(例えば10分間)放置し、誘導体化反応を行なう。
(3)窒素雰囲気下で試料溶液に氷酢酸を添加し、誘導体化反応を停止させる。
(4)所定の洗浄液(例えば、クロロホルム:メタノール:水=8:4:3の混合液)を試料溶液に添加して混合した後、遠心分離して下層を回収する。同様の洗浄を複数回繰り返してもよい。最後に試料溶液にメタノール:水=9:1の溶液を添加する。
(5)窒素雰囲気下で試料溶液を乾固する。その後、試料に所定量のメタノールを添加し、超音波で溶解させる。さらに所定量の水を試料に添加する。
4,6,15 送液ポンプ
8 試料注入部
10 分離カラム
12 背圧制御器(BPR)
14 質量分析計(MS)
Claims (5)
- β-シクロデキストリンを含む分離媒体が内部に充填された分離カラムを有する超臨界流体クロマトグラフの分析流路中に複数種類の生体膜ホスホイノシタイドを含む試料を注入し、超臨界流体クロマトグラフィーによって前記複数種類の生体膜ホスホイノシタイドを互いに分離する分離ステップを備える生体膜ホスホイノシタイドの分離方法。
- 前記複数種類の生体膜ホスホイノシタイドが、生体膜ホスホイノシタイドの複数の異性体を含む、請求項1に記載の分離方法。
- 前記複数の異性体が、PI(3)P、PI(4)P、PI(5)P、PI(3,4)P2、PI(3,5)P2、PI(4,5)P2、PI(3,4,5)P3のいずれかである、請求項2に記載の分離方法。
- 前記分離ステップの前に、前記複数種類の生体膜ホスホイノシタイドのリン酸基をトリメチルシリル-ジアゾメタンによって誘導体化する誘導体化ステップを備え、
前記分離ステップの後、前記分離カラムで分離された前記複数種類の生体膜ホスホイノシタイドをそれぞれ質量分析計により検出する検出ステップを備えている、請求項1に記載の分離方法。 - 前記分離ステップでは、ギ酸メタノール水溶液をモディファイアとして用いる、請求項1に記載の分離方法。
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AU2019340961A AU2019340961B2 (en) | 2018-09-10 | 2019-08-30 | Biological membrane phosphoinositide separation method |
JP2020545914A JP7017704B2 (ja) | 2018-09-10 | 2019-08-30 | 生体膜ホスホイノシタイドの分離方法 |
CN201980046921.2A CN112424596B (zh) | 2018-09-10 | 2019-08-30 | 生物膜磷酸肌醇的分离方法 |
US17/272,973 US20210310999A1 (en) | 2018-09-10 | 2019-08-30 | Biological membrane phosphoinositide separation method |
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Citations (2)
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