WO2003008962A1 - Verfahren zur quantitativen bestimmung von dicarbonylverbindungen - Google Patents
Verfahren zur quantitativen bestimmung von dicarbonylverbindungen Download PDFInfo
- Publication number
- WO2003008962A1 WO2003008962A1 PCT/EP2002/007623 EP0207623W WO03008962A1 WO 2003008962 A1 WO2003008962 A1 WO 2003008962A1 EP 0207623 W EP0207623 W EP 0207623W WO 03008962 A1 WO03008962 A1 WO 03008962A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- carbonyl
- compound
- detection reagent
- antibody
- dicarbonyl
- Prior art date
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- 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
- G01N33/5308—Immunoassay; Biospecific binding assay; Materials therefor for analytes not provided for elsewhere, e.g. nucleic acids, uric acid, worms, mites
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/20—Oxygen containing
- Y10T436/200833—Carbonyl, ether, aldehyde or ketone containing
Definitions
- the present invention relates to a method for the quantitative determination of dicarbonyl compounds in gaseous and / or liquid samples and erosols.
- the method can also be used to determine the accumulation of reactive carbonyl compounds in the so-called carbonyl stress of diabetics.
- Methylglyoxal can arise from triose phosphate, the metabolism of ketone bodies and the metabolism of threonine and is further broken down by glyoxalase. Methylglyoxal then reacts with proteins to form iridazolone derivatives and bis-lysyl cross-links. This cross-linking of the proteins can lead to the stabilization of collagen and thus to the thickening of membranes. These reactions explain at least part of the diabetic complications such as kidney failure and lens opacification.
- ⁇ -oxoaldehydes are therefore invasive with one exception, ie from the blood plasma.
- patients with insulin-dependent diabetes, Thornally TJ, "Advanced Glycation and the development of diabetic complications / Unifying the involvement of Glucose, methylglyoxal and oxidative stress" Endocrinology and Metabolism, 1996, 3, 149-166 directly in plasma compared to healthy comparison subjects, five to six times higher, in patients with insulin-dependent diabetes, a two to three times higher methylglyoxal concentration can be detected.
- a determination of ⁇ -oxoaldehyde in the urine would be possible, but is not described in the literature, since the expected physiologically very low concentrations in the urine increase would require a lot of analysis, therefore a direct determination of the ⁇ -oxoaldehydes in the plasma is required.
- methylglyoxal plays a role in the pathogenesis of Alzheimer's syndrome and vascular diseases. This opens up further areas of application for breathing air or breathing condensate diagnostics.
- a method for the quantitative determination of dicarbonyl compounds in gaseous and / or liquid samples and aerosols which includes the following steps:
- the method is carried out using microtiter plates.
- microtiter plates which are suitable for the coupling of dicarbonyl compounds can be used, and the surface of the microtiter plates can be derivatized so that the desired functionality for binding the dicarbonyl compounds is obtained.
- the method can also be carried out with the aid of a flow injection system (FIA).
- FSA flow injection system
- the sample and other reagents are injected in a carrier stream that is transported using peristaltic pumps.
- peristaltic pumps peristaltic pumps
- other miniaturized flow systems are also possible.
- the method can also be carried out using a cartridge.
- the sample is passed through a cartridge containing the solid phase, e.g. with the help of a syringe.
- the dicarbonyl compounds in the cartridge are bound to the solid phase and can then be detected either internally or externally.
- the solid phase can be present both as a porous material or in particle form.
- step a) the coupling reaction between a first carbonyl function and the carbonyl-reactive group is preferred, and then in step b) a coupling reaction between a detection reagent and the second, not yet bound carbonyl function which carries out the carbonyl compound.
- step b) a fluorophoric hydrazide is preferably used as the detection reagent, which is subsequently detected fluorometrically in step c). Examples of fluorophore hydrazides are the following connections in question:
- a compound containing hydrazide groups can also be used in step b), which can then be mixed with an additive specific for this compound.
- antibody is coupled.
- This antibody can preferably be used with a detection reagent, e.g. B. a fluorophore, gold or latex particles, are marked.
- the antibody can be labeled with an enzyme as a detection molecule.
- an additional variant is the use of an avidin-enzyme complex as a detection reagent.
- a biotin hydrazide is bound to the second carbonyl function of the dicarbonyl compound, and an enzyme can be coupled via the biotin-avidin interaction.
- the use of avidin makes it possible to amplify the signal by crosslinking the avidin-enzyme conjugates with a diotin because of its four-bond nature. This cross-linking can take place in advance.
- an enzyme When an enzyme is coupled in step c), it is preferably detected photometrically, fluorometrically, electrochemically and / or luminometrically.
- a further variant for the detection consists in that a high-molecular compound is coupled to the dicarbonyl compound and this is then detected on the basis of the increase in mass.
- quartz microwaves or direct optical methods such as surface plason resonance (English: surface plas on resonance, SPR) come into question.
- a further variant for the detection consists in using in step b) nano- or microparticles which are suitable for optical detection and which carry carbonyl-reactive groups on their surface. These react with the second carbonyl function of the dicarbonyl compound.
- the detection can be carried out photometrically, fluorimetrically, nephelometrically, turbidimetrically or visually.
- a coupling reaction between the immobilized compound formed during the enrichment and a specific detection reagent can take place in step b).
- Compounds from the group of the aminopyrazines, aminopyridines, aminopyrimidines and aminoguanidines are preferably selected as carbonyl-reactive groups. These compounds are able to covalently bind the carbonyl compounds such as methylglyoxal or glyoxal via their two carbonyl groups. In this variant, these compounds are therefore immobilized on the solid phase, so that they subsequently serve as a scavenger component for the dicarbonyl compounds.
- the component formed as a result of the reaction between the dicarbonyl compound and the said compounds can then be detected using an antibody which is specific for this component.
- this antibody is not reactive with the free dicarbonyl compounds or the capture component.
- the antibody can be labeled with a detection molecule, for which fluorophores, enzymes, latex or gold particles are suitable. It is also possible for the antibody to be detected with the aid of an anti-antibody or via the avidin-biotin system.
- the solid phase or the water-soluble polymer, which are derivatized with carbonyl-reactive groups serve as a specific detection reagent, an aromatic component being formed by a ring closure reaction. This in turn can then be detected photometrically or fluorometrically in step c).
- the detectable product is created independently by the two-stage coupling reaction without further coupling of an additional detection reagent.
- ⁇ -Oxoaldehydes are determined as the preferred dicarbonyl compound using the method. This particularly preferably includes methylglyoxal, glyoxal and / or 3-deoxyglucuron.
- the method is carried out in gaseous and liquid samples and examples include breathing air, breathing condensate, saliva, broncheo-alveolar lavage,
- dicarbonyl compounds here methylglyoxal (1)
- solid phase derivatized with hydrazide groups are coupled to the solid phase derivatized with hydrazide groups.
- Acetone (2) as a monocarbonyl compound is also bound to the solid phase, but has no further free carbonyl function for coupling the Detection reagent, whereby the monocarbonyl compounds are not detected and a disturbance by them is avoided.
- the subsequent coupling of the enzyme takes place in two ways.
- the dicarbonyl compound reacts via the second, still free carbonyl function with a biotin (5) which is bound to a hydrazide.
- the biotin (5) is coupled with an avidin molecule (3), to which an enzyme (4) is in turn bound.
- an enzyme (4) modified with a hydrazide group is bound directly.
- Fig. 3 shows the principle of detection of the component formed due to the reaction between the dicarbonyl compound and the carbonyl-reactive capture component by means of a specific antibody.
- Methylglyoxal (1) reacts with the capture component (2) immobilized on the solid phase (3) to form a component (4), which is detected by a specific antibody (5) which is provided with a label (6).
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Chemical & Material Sciences (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Medicinal Chemistry (AREA)
- Analytical Chemistry (AREA)
- Cell Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Food Science & Technology (AREA)
- Biotechnology (AREA)
- Physics & Mathematics (AREA)
- Microbiology (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)
- Investigating Or Analysing Materials By The Use Of Chemical Reactions (AREA)
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002454052A CA2454052A1 (en) | 2001-07-16 | 2002-07-09 | Method for quantitative determination of dicarbonyl compounds |
EP02787122A EP1407260A1 (de) | 2001-07-16 | 2002-07-09 | Verfahren zur quantitativen bestimmung von dicarbonylverbindungen |
US10/483,944 US20050014276A1 (en) | 2001-07-16 | 2002-07-09 | Method for quatitative determination of dicarbonyl compounds |
JP2003514253A JP2004535583A (ja) | 2001-07-16 | 2002-07-09 | ジカルボニル合成物の定量法 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE10134568A DE10134568C2 (de) | 2001-07-16 | 2001-07-16 | Verfahren zur quantitativen Bestimmung von alpha-Oxoaldehyd |
DE10134568.2 | 2001-07-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2003008962A1 true WO2003008962A1 (de) | 2003-01-30 |
Family
ID=7691979
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2002/007623 WO2003008962A1 (de) | 2001-07-16 | 2002-07-09 | Verfahren zur quantitativen bestimmung von dicarbonylverbindungen |
Country Status (6)
Country | Link |
---|---|
US (1) | US20050014276A1 (de) |
EP (1) | EP1407260A1 (de) |
JP (1) | JP2004535583A (de) |
CA (1) | CA2454052A1 (de) |
DE (1) | DE10134568C2 (de) |
WO (1) | WO2003008962A1 (de) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE10028548C1 (de) * | 2000-06-09 | 2001-08-30 | Inst Chemo Biosensorik | Verfahren zum Nachweis von alpha-Oxoaldehyden in Vollblut, Blutplasma und/oder Serum eines Patienten |
WO2001089478A1 (en) * | 2000-05-25 | 2001-11-29 | Gambro Lundia Ab | Carbohydrate medical solution and sulphite stabilisator in a multiple compartment container and use thereof |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4786287A (en) * | 1986-10-10 | 1988-11-22 | Baxter Travenol Laboratories | Process for decreasing residual aldehyde levels in implantable bioprosthetic tissue |
US5132242A (en) * | 1987-07-15 | 1992-07-21 | Cheung Sau W | Fluorescent microspheres and methods of using them |
US5512659A (en) * | 1989-08-04 | 1996-04-30 | Syntex (U.S.A.) Inc. | Compositions useful in heterogeneous immunoassays |
US5744451A (en) * | 1995-09-12 | 1998-04-28 | Warner-Lambert Company | N-substituted glutamic acid derivatives with interleukin-1 β converting enzyme inhibitory activity |
-
2001
- 2001-07-16 DE DE10134568A patent/DE10134568C2/de not_active Expired - Fee Related
-
2002
- 2002-07-09 JP JP2003514253A patent/JP2004535583A/ja active Pending
- 2002-07-09 WO PCT/EP2002/007623 patent/WO2003008962A1/de not_active Application Discontinuation
- 2002-07-09 EP EP02787122A patent/EP1407260A1/de not_active Withdrawn
- 2002-07-09 US US10/483,944 patent/US20050014276A1/en not_active Abandoned
- 2002-07-09 CA CA002454052A patent/CA2454052A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001089478A1 (en) * | 2000-05-25 | 2001-11-29 | Gambro Lundia Ab | Carbohydrate medical solution and sulphite stabilisator in a multiple compartment container and use thereof |
DE10028548C1 (de) * | 2000-06-09 | 2001-08-30 | Inst Chemo Biosensorik | Verfahren zum Nachweis von alpha-Oxoaldehyden in Vollblut, Blutplasma und/oder Serum eines Patienten |
Non-Patent Citations (4)
Title |
---|
DATABASE BIOSIS [online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1994, YAMAGUCHI MASATOSHI ET AL: "Determination of glyoxal, methylglyoxal, diacetyl, and 2,3-pentanedione in fermented foods by high-performance liquid chromatography with fluorescence detection.", XP002215389, Database accession no. PREV199497544134 * |
JOURNAL OF LIQUID CHROMATOGRAPHY, vol. 17, no. 1, 1994, pages 203 - 211, ISSN: 0148-3919 * |
LIU L J S (REPRINT) ET AL: "Evaluation of media and derivatization chemistry for six aldehydes in a passive sampler", ENVIRONMENTAL SCIENCE & TECHNOLOGY, (1 JUN 2001) VOL. 35, NO. 11, PP. 2301-2308. PUBLISHER: AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036 USA. ISSN: 0013-936X., Univ Washington, Dept Environm Hlth, Box 357234, Seattle, WA 98195 USA (Reprint);Univ Washington, Dept Environm Hlth, Seattle, WA 98195 USA, XP002215387 * |
SCHRAMM C (REPRINT) ET AL: "Determination of cotton-bound glyoxal via an internal Cannizzaro reaction by means of high-performance liquid chromatography", ANALYTICAL CHEMISTRY, (1 DEC 2000) VOL. 72, NO. 23, PP. 5829-5833. PUBLISHER: AMER CHEMICAL SOC, 1155 16TH ST, NW, WASHINGTON, DC 20036. ISSN: 0003-2700., LEOPOLD FRANZENS UNIV INNSBRUCK, INST TEXT CHEM & TEXT PHYS, A-6850 DORNBIRN, AUSTRIA (Reprint), XP002215388 * |
Also Published As
Publication number | Publication date |
---|---|
EP1407260A1 (de) | 2004-04-14 |
JP2004535583A (ja) | 2004-11-25 |
DE10134568C2 (de) | 2003-07-24 |
US20050014276A1 (en) | 2005-01-20 |
CA2454052A1 (en) | 2003-01-30 |
DE10134568A1 (de) | 2003-02-06 |
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