DE69304511T2 - Testverfahren für homocysteine - Google Patents
Testverfahren für homocysteineInfo
- Publication number
- DE69304511T2 DE69304511T2 DE69304511T DE69304511T DE69304511T2 DE 69304511 T2 DE69304511 T2 DE 69304511T2 DE 69304511 T DE69304511 T DE 69304511T DE 69304511 T DE69304511 T DE 69304511T DE 69304511 T2 DE69304511 T2 DE 69304511T2
- Authority
- DE
- Germany
- Prior art keywords
- adenosine
- antibody
- adenosylhomocysteine
- sample
- analyte
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000010998 test method Methods 0.000 title 1
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- 239000002126 C01EB10 - Adenosine Substances 0.000 claims description 94
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- ZJUKTBDSGOFHSH-WFMPWKQPSA-N S-Adenosylhomocysteine Chemical compound O[C@@H]1[C@H](O)[C@@H](CSCC[C@H](N)C(O)=O)O[C@H]1N1C2=NC=NC(N)=C2N=C1 ZJUKTBDSGOFHSH-WFMPWKQPSA-N 0.000 claims description 57
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- C12Q1/48—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
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- C07H15/14—Acyclic radicals, not substituted by cyclic structures attached to a sulfur, selenium or tellurium atom of a saccharide radical
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- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
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- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
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Claims (36)
1. Verfahren zur Bestimmung des Homocysteingehaltes einer
Probe, wobei man (a) die Probe mit dem Enzym
S-Adenosylhomocysteinhydrolase und mit wenigstens einer Verbindung,
ausgewählt unter (i) S-Adenosylhomocystein und (ii)
Adenosin oder einem Adenosinanalogen, in Kontakt bringt und (b)
einen nicht-markierten Analyten, der ausgewählt ist unter
Adenosin, dem Adenosinanalogen und S-Adenoeylhomocystein,
ohne chromatographische Trennung bestimmt.
2. Verfahren nach Anspruch 1, wobei die Probe mit einem
Antikörper gegen den Analyten und mit einem Hapten für den
Antikörper in Kontakt gebracht wird, das von dem
nichtmarkierten Analyten verschieden ist, und wobei die
Bestimmung des Analyten indirekt durch Bestimmung des an den
Antikörper gebundenen bzw. nicht gebundenen Haptens
erfolgt.
3. Verfahren nach Anspruch 2, wobei das Hapten ein Polyhapten
ist.
4. Verfahren nach Anspruch 2, wobei das Hapten ein markiertes
Molekül ist, welches eine auch in dem nicht-markierten
Analyten vorhandene Epitop-Struktureinheit aufweist.
5. Verfahren nach einem der Ansprüche 2 bis 4, wobei der
Antikörper ein monoklonaler Antikörper ist.
6. Verfahren nach einem der Ansprüche 2 bis 5, wobei der
Antikörper ein an eine Trägermatrix gebundener Antikörper
ist.
7. Verfahren nach Anspruch 1, wobei die Probe mit einem
zweiten Enzym in Kontakt gebracht wird, das zur Umwandlung des
Analyten dient, und wobei die Bestimmung des Analyten
indirekt, durch Bestimmung eines von dem Analyten verschie
denen Substrates des zweiten Enzyms oder eines Produktes
der enzymatischen Umwandlung des Analyten durch das zweite
Enzym, erfolgt.
8. Verfahren nach einem der Ansprüche 1 bis 7, wobei der
Analyt Adenosin ist.
9. Verfahren nach Anspruch 8, wobei die Probe zusätzlich mit
einem von S-Adenosylhomocysteinhydrolase verschiedenen,
Adenosin-umwandelnden Enzym in Kontakt gebracht wird, und
wobei es sich bei dem Analyten um Adenosin handelt und die
Bestimmung des Adenosins indirekt, durch Bestimmung eines
Co-Substrates oder eines Reaktionsproduktes der
Adenosinumwandlung durch das Adenosin-umwandelnde Enzym, erfolgt.
10. Verfahren nach Anspruch 9, wobei das Adenosin-umwandelnde
Enzym Adenosinkinase ist.
11. Verfahren nach Anspruch 9, wobei das Adenosin-umwandelnde
Enzym Adenosindeaminase ist.
12. Verfahren nach einem der Ansprüche 1 bis 7, wobei der
Analyt S-Adenosylhomocystein ist.
13. Verfahren nach einem der Ansprüche 1 bis 12, wobei die
Probe eine Blut-, Plasma- oder Urinprobe ist, die mit
einem Disulfidbindungen spaltenden Reduktionsmittel
vorbehandelt wurde.
14. Verfahren nach einem der Ansprüche 1 bis 13, wobei die
Bestimmung des Analyten photometrisch erfolgt.
15. Verfahren nach Anspruch 14, wobei die Bestimmung
spektrometrisch oder colorimetrisch erfolgt.
16. Verfahren nach Anspruch 14, wobei die Bestimmung
turbidimetrisch oder nephelometrisch erfolgt.
17. Verfahren nach Anspruch 14, wobei die Bestimmung mittels
Fluoreszenzpolarisationsdetektion erfolgt.
18. Verfahren nach einem der Ansprüche 1 bis 7, 12 bis 15 und
17, wobei die Bestimmung des Analyten indirekt, durch
Detektion eines Chromophors oder Fluorophors auf markiertem
S-Adenosylhomocystein oder auf einem markierten Furanose-
6-thioether, erfolgt.
19. Verfahren nach Anspruch 1, wobei man eine Blut-,
Plasma- oder Urinprobe mit einem Reduktionsmittel behandelt; die
Probe mit Adenosin und S-Adenosylhomocysteinhydrolase in
Kontakt bringt; das resultierende Gemisch inkubiert und
dann mit ATP und Adenosinkinase in Kontakt bringt und das
Gemisch wenigstens eine Minute inkubiert; das
resultierende Gemisch mit Luciferin und Luciferase in Kontakt bringt
und das dabei erzeugte Licht detektiert.
20. Verfahren nach Anspruch 1, wobei man eine Blut-,
Plasma- oder Urinprobe mit einem Reduktionsmittel behandelt; die
Probe mit Adenosin und S-Adenosylhomocysteinhydrolase in
Kontakt bringt; das resultierende Gemisch inkubiert und
dann mit Adenosindeaminase, Nucleosidphosphorylase,
Xanthinoxidase und einer Peroxidase in Kontakt bringt und die
UV-Absorption des Gemisches bestimmt.
21. Verfahren nach Anspruch 1, wobei man die Probe mit
Adenosin und einer S-Adenosylhomocysteinhydrolase in Kontakt
bringt; das resultierende Gemisch inkubiert und dann mit
einem Fluorophor-markierten S-Adenosylhomocystein oder
einem Fluorophor-markierten Furanose-6-thioether in
Kontakt bringt; das resultierende Gemisch mit einem
monoklonalen Anti-S-Adenosylhomocystein-Antikörper in Kontakt
bringt; und die an den Antikörper gebundene bzw. nicht an
den Antikörper gebundene, Fluorophor-markierte Verbindung
durch Fluoreszenzpolarisation bestimmt, um einen Hinweis
auf den anfänglichen Homocysteingehalt der Probe zu
erhalten.
22. Verfahren nach Anspruch 1, wobei man die Probe mit
Adenosin und einer S-Adenosylhomocysteinhydrolase in Kontakt
bringt; das resultierende Gemisch inkubiert und dann mit
einem markierten S-Adenosylhomocystein oder einem
markierten Furanose-6-thioether in Kontakt bringt; das
resultierende Gemisch mit einem an eine Trägermatrix gebundenen
monoklonalen Anti-S-Adenosylhomocystein-Antikörper in
Kontakt bringt; die Antikörper-Trägermatrix wäscht; und die
an den Antikörper gebundene, markierte Verbindung
photometrisch bestimmt, um einen Hinweis auf den anfänglichen
Homocysteingehalt der Probe zu erhalten.
23. Verfahren nach Anspruch 22, wobei die Markierung der an
den Antikörper gebundenen, markierten Verbindung zu einem
Chromophor umgesetzt wird, der dann photometrisch bestimmt
wird.
24. Verfahren nach Anspruch 3, wobei die Bestimmung durch
Bestimmung der Präzipitation oder Agglutination von
Antikörper: Polyhapten-Konjugaten erfolgt.
25. Analytischer Kit zur Verwendung für den Homocystein-Assay
in einer Probe durch das Verfahren gemäß Anspruch 1, wobei
der Kit umfaßt; S-Adenosylhomocysteinhydrolase; ein
Substrat, das ausgewählt ist unter Adenosin, Adenosinanaloga
und S-Adenosylhomocystein; ein Signal-erzeugendes Mittel;
und gegebenenfalls Mittel zur Signalbestimmung.
26. Kit nach Anspruch 25, umfassend:
S-Adenosylhomocysteinhydrolase; markiertes S-Adenosylhomocystein als ein Signal
erzeugendes Substrat für das Enzym; einen gegebenenfalls
an eine Trägermatrix gebundenen
Anti-S-Adenosylhomocystein-Antikörper; und gegebenenfalls, als Mittel zur
Signalbestimmung, Mittel zur photometrischen Bestimmung des
markierten S-Adenosylhomocysteins oder des detektierbaren
Derivates davon, um einen Hinweis auf den
Homocysteingehalt der Probe zu erhalten.
27. Kit nach Anspruch 25, umfassend:
S-Adenosylhomocysteinhydrolase; Adenosin; ein von S-Adenosylhomocysteinhydrolase
verschiedenes, Adenosin-umwandelndes Enzym; gegebenenfalls
ein Adenosin-Cosubstrat für das Adenosin-umwandelnde
Enzym; und, als Mittel zur Signalbestimmung, Mittel zur
Erzeugung einer photometrisch detektierbaren Antwort des
Cosubstrates oder eines Produktes der enzymatischen
Umwandlung von Adenosin mit dem Adenosin-umwandelnden Enzym.
28. Kit nach Anspruch 27, worin das Adenosin-umwandelnde Enzym
Adenosinkinase ist und worin das erzeugende Mittel ATP,
Luciferin und eine Luciferase umfaßt.
29. Kit nach Anspruch 27, worin das Adenosin-umwandelnde Enzym
Adenosindeaminase ist und das erzeugende Mittel Nucleosid
phosphorylase, Xanthinoxidase und eine Peroxidase umfaßt.
30. Kit nach Anspruch 27, umfassend:
S-Adenosylhomocysteinhydrolase; Adenosin; einen gegebenenfalls an Matrixpartikel
gebundenen Anti-S-Adenosylhomocystein-Antikörper; ein
Polyhapten für den Antikörper; und-gegebenenfalls, als
Mittel zur Signalbestimmung, Mittel zur photometrischen
Bestimmung der Agglutination oder Präzipitation von
Antikörper: Polyhapten-Komplexen.
31. Verfahren nach Anspruch 2, wobei als Hapten eine
Verbindung der Formel I
(worin R&sub1; und R&sub2; gleich oder verschieden sind und für
Wasserstoffatome oder OR&sub4;-Gruppen stehen, oder R&sub1; und R&sub2;
zusammen für ein Sauerstoffatom stehen, R&sub3; für eine
Aminooder Carboxylgruppe und R&sub4; für eine aliphatische
C&sub1;&submin;&sub6;-Gruppe steht) oder ein Salz oder Ester davon verwendet
wird.
32. Verfahren nach Anspruch 4, wobei als Hapten ein markierter
Furanose-6-thioether verwendet wird, worin die markierte
Einheit einen Chromophor oder Fluorophor oder ein
radioaktives Atom umfaßt und worin die Thioethereinheit eine
Trimethylenthio-Einheit umfaßt.
33. Verfahren nach Anspruch 32, wobei als markierter Thioether
eine markierte Verbindung der in Anspruch 31 definierten
Formel I verwendet wird.
34. Verfahren nach Anspruch 1, wobei als Enzym inaktivierte
SAH-Hydrolase verwendet wird, die durch Kontakt mit einein
Reduktionsmittel aktiviert wird.
35. Kit nach Anspruch 25, uinfassend, in einem ersten
Kompartiment, inaktive SAH-Hydrolase und, in einem zweiten
Kompartiment, ein Reduktionsmittel, wobei man durch Vermischen
der Inhalte des ersten und zweiten Kompartiments
aktivierte SAH-Hydrolase erzeugt.
36. Kit nach Anspruch 35, worin das zweite Kompartiment
Dithiothreitol in einem sauren Medium umfaßt.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO920282A NO920282D0 (no) | 1992-01-22 | 1992-01-22 | Fremgangsmaate ved proeving av cystein |
| US83311892A | 1992-02-10 | 1992-02-10 | |
| GB929204922A GB9204922D0 (en) | 1992-03-06 | 1992-03-06 | Assay |
| PCT/GB1993/000138 WO1993015220A1 (en) | 1992-01-22 | 1993-01-22 | Homocysteine assay |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69304511D1 DE69304511D1 (de) | 1996-10-10 |
| DE69304511T2 true DE69304511T2 (de) | 1997-01-23 |
Family
ID=27266081
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69304511T Expired - Lifetime DE69304511T2 (de) | 1992-01-22 | 1993-01-22 | Testverfahren für homocysteine |
| DE69332891T Expired - Lifetime DE69332891T3 (de) | 1992-01-22 | 1993-01-22 | Testverfahren für Homocysteine |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69332891T Expired - Lifetime DE69332891T3 (de) | 1992-01-22 | 1993-01-22 | Testverfahren für Homocysteine |
Country Status (18)
| Country | Link |
|---|---|
| EP (2) | EP0726322B2 (de) |
| JP (1) | JP2870704B2 (de) |
| AT (2) | ATE142271T1 (de) |
| AU (1) | AU676480B2 (de) |
| BR (1) | BR9305780A (de) |
| CA (1) | CA2128512C (de) |
| CZ (1) | CZ287334B6 (de) |
| DE (2) | DE69304511T2 (de) |
| DK (2) | DK0726322T4 (de) |
| ES (2) | ES2094524T3 (de) |
| FI (1) | FI106728B (de) |
| GR (1) | GR3021365T3 (de) |
| HU (1) | HU219607B (de) |
| NO (1) | NO314946B1 (de) |
| PT (1) | PT726322E (de) |
| RU (1) | RU2121001C1 (de) |
| SK (1) | SK281517B6 (de) |
| WO (1) | WO1993015220A1 (de) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5478729A (en) * | 1994-04-28 | 1995-12-26 | Syntex (U.S.A.) Inc. | Immunoassay for homocysteine |
| GB9617683D0 (en) | 1996-08-23 | 1996-10-02 | Univ Glasgow | Homocysteine desulphurase |
| DE19713088C1 (de) * | 1997-03-27 | 1998-11-26 | Reiner Dr Probst | Verfahren und Blutabnahmegefäß zur Aufbereitung von Blutproben für die Homocystein- und/oder Folatbestimmung |
| WO1998059242A1 (en) * | 1997-06-23 | 1998-12-30 | Nexstar Pharmaceuticals, Inc. | Homocysteine assay |
| US5985540A (en) * | 1997-07-24 | 1999-11-16 | Anticancer, Inc. | High specificity homocysteine assays for biological samples |
| US6066467A (en) * | 1997-07-24 | 2000-05-23 | Anticancer, Inc. | High specificity homocysteine assays for biological samples |
| US6468762B1 (en) | 1997-07-24 | 2002-10-22 | Anticancer, Inc. | High specificity homocysteinases |
| US6140102A (en) * | 1997-07-24 | 2000-10-31 | Anticancer, Inc. | High specificity homocysteinases and genes therefor |
| AU4835599A (en) | 1998-06-29 | 2000-01-17 | Edwin F. Ullman | Assay for homocysteine |
| GB9900159D0 (en) * | 1999-01-05 | 1999-02-24 | Axis Biochemicals Asa | Assay |
| AU2404500A (en) * | 1999-01-08 | 2000-07-24 | Medical Analysis Systems, Inc. | Compositions and methods for stabilizing thiol-containing biomolecules |
| EP1157128B1 (de) | 1999-02-01 | 2007-12-05 | Anticancer, Inc. | Homogene enzymatische bestimmungsmethode für vitamin b6 |
| US6376210B1 (en) | 1999-07-06 | 2002-04-23 | General Atomics | Methods and compositions for assaying analytes |
| CA2377665A1 (en) * | 1999-07-06 | 2001-01-11 | General Atomics | Methods and compositions for assaying analytes |
| US7192729B2 (en) | 1999-07-06 | 2007-03-20 | General Atomics | Methods for assaying homocysteine |
| GB0008784D0 (en) | 2000-04-10 | 2000-05-31 | Axis Shield Plc | Assay |
| US6610504B1 (en) | 2000-04-10 | 2003-08-26 | General Atomics | Methods of determining SAM-dependent methyltransferase activity using a mutant SAH hydrolase |
| JP4807920B2 (ja) * | 2000-06-30 | 2011-11-02 | アルフレッサファーマ株式会社 | 総ホモシステイン測定方法 |
| EP1592813B1 (de) * | 2003-01-30 | 2012-12-26 | BellBrook Labs, LLC | Testverfahren für gruppenübertragungsreaktionen |
| JP2006149203A (ja) * | 2003-02-19 | 2006-06-15 | Alfresa Pharma Corp | ホモシステインの測定方法 |
| US7097968B2 (en) * | 2003-07-10 | 2006-08-29 | General Atomics | Methods and compositions for assaying homocysteine |
| US8476034B2 (en) | 2003-07-10 | 2013-07-02 | General Atomics | Methods and compositions for assaying homocysteine |
| US7384760B2 (en) | 2004-04-30 | 2008-06-10 | General Atomics | Methods for assaying inhibitors of S-adenosylhomocysteine (SAH) hydrolase and S-adenosylmethionine (SAM)-dependent methyltransferase |
| GB0503836D0 (en) * | 2005-02-24 | 2005-04-06 | Axis Shield Asa | Method |
| JP2007170992A (ja) * | 2005-12-22 | 2007-07-05 | Abbott Japan Co Ltd | ホモシステインの免疫学的測定方法 |
| JP5803104B2 (ja) * | 2010-12-28 | 2015-11-04 | 東ソー株式会社 | 安定化されたｓ−アデノシルホモシステイン加水分解酵素調製物 |
| JP6056138B2 (ja) | 2010-12-28 | 2017-01-11 | 東ソー株式会社 | 免疫学的測定方法 |
| JP5919914B2 (ja) * | 2012-03-15 | 2016-05-18 | 東ソー株式会社 | ホモシステイン測定用前処理試薬 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5811857A (ja) * | 1981-07-15 | 1983-01-22 | Yamasa Shoyu Co Ltd | アデノシンの定量法 |
| JPS6030679A (ja) * | 1983-07-29 | 1985-02-16 | Nippon Zeon Co Ltd | Ｓ−アデノシル−ｌ−ホモシステインハイドロラ−ゼの製造法 |
-
1993
- 1993-01-22 DE DE69304511T patent/DE69304511T2/de not_active Expired - Lifetime
- 1993-01-22 ES ES93902437T patent/ES2094524T3/es not_active Expired - Lifetime
- 1993-01-22 AU AU43408/93A patent/AU676480B2/en not_active Ceased
- 1993-01-22 JP JP5513023A patent/JP2870704B2/ja not_active Expired - Lifetime
- 1993-01-22 WO PCT/GB1993/000138 patent/WO1993015220A1/en active IP Right Grant
- 1993-01-22 ES ES96200534T patent/ES2196116T5/es not_active Expired - Lifetime
- 1993-01-22 CZ CZ19941763A patent/CZ287334B6/cs not_active IP Right Cessation
- 1993-01-22 EP EP96200534A patent/EP0726322B2/de not_active Expired - Lifetime
- 1993-01-22 DK DK96200534.4T patent/DK0726322T4/da active
- 1993-01-22 SK SK878-94A patent/SK281517B6/sk unknown
- 1993-01-22 DE DE69332891T patent/DE69332891T3/de not_active Expired - Lifetime
- 1993-01-22 PT PT96200534T patent/PT726322E/pt unknown
- 1993-01-22 RU RU94038061A patent/RU2121001C1/ru not_active IP Right Cessation
- 1993-01-22 AT AT93902437T patent/ATE142271T1/de active
- 1993-01-22 AT AT96200534T patent/ATE237696T1/de active
- 1993-01-22 CA CA002128512A patent/CA2128512C/en not_active Expired - Lifetime
- 1993-01-22 BR BR9305780A patent/BR9305780A/pt not_active IP Right Cessation
- 1993-01-22 DK DK93902437.8T patent/DK0623174T3/da active
- 1993-01-22 EP EP93902437A patent/EP0623174B1/de not_active Expired - Lifetime
- 1993-01-22 HU HU9402170A patent/HU219607B/hu unknown
-
1994
- 1994-07-21 NO NO19942729A patent/NO314946B1/no not_active IP Right Cessation
- 1994-07-21 FI FI943462A patent/FI106728B/fi not_active IP Right Cessation
-
1996
- 1996-10-16 GR GR960402738T patent/GR3021365T3/el unknown
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