Claims
- 1. A method for measuring an adenyl group-containing substance which comprises:
- (i) deriving a chemiluminescent substance by reacting a compound represented by the following formula 1 with an adenyl group in the substance to be measured, in the presence of an acid catalyst;
- R.sup.1 --CO--R.sup.2 ( 1)
- wherein R.sup.1 is a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an aryl group having 1 to 18 carbon atoms or an aromatic heterocyclic group having 1 to 18 carbon atoms;
- wherein said R.sup.1 may be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group; and
- the group itself which substitutes or ring-condenses the R.sup.1 may be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group;
- and wherein
- R.sup.2 is an aldehyde group or a group represented by --CH(OR.sup.3)(OR.sup.4) in which R.sup.3 and R.sup.4 are the same or different groups which may form a ring by their partial binding and are selected from a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, and an aryl group having 1 to 18 carbon atoms;
- wherein said R.sup.3 and R.sup.4 can be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group; and
- the group itself which substitutes or ring-condenses the R.sup.3 and R.sup.4 groups can be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group;
- and
- (ii) qualitatively or quantitatively measuring said substance to be measured using luminescent intensity obtained from said chemiluminescent substance as an index.
- 2. The method of claim 1, wherein said adenyl group-containing substance is adenine, adenosine, an adenosine phosphate compound, DNA containing at least one adenine moiety or RNA containing at least one adenine moiety.
- 3. The method of claim 1, which further comprises a step (ia) of contacting the chemiluminescent substance derived in step (i) with a hydroxide solution initiator.
- 4. The method of claim 3, wherein said hydroxide solution is a sodium hydroxide solution.
- 5. The method of claim 3, wherein said contacting step (ia) is performed in a polar solvent selected from the group consisting of dimethylformamide, isopropanol, acetonitrile, dioxane, dimethylsulfoxide and water.
- 6. The method of claim 1, wherein R.sup.1 is a phenyl group.
- 7. The method of claim 6, which further comprises a step (ia) of contacting the chemiluminescent substance derived in step (i) with a hydroxide solution initiator.
- 8. The method of claim 7, wherein said hydroxide solution is a sodium hydroxide solution.
- 9. The method of claim 8, wherein said contacting step (ia) is performed in a polar solvent selected from the group consisting of dimethylformamide, isopropanol, acetonitrile, dioxane, dimethyl sulfoxide and water.
- 10. The method of claim 1, wherein R.sup.1 is an alkyl group.
- 11. The method of claim 10, which further comprises a step (ia) of contacting the chemiluminescent substance derived in step (i) with a hydroxide solution initiator.
- 12. The method of claim 11, wherein said hydroxide solution sodium hydroxide solution.
- 13. The method of claim 12, wherein said contacting step (ia) is performed in a polar solvent selected from the group consisting of dimethylformamide, isopropanol, acetonitrile, dioxane, dimethyl sulfoxide and water.
- 14. A method for measuring an adenyl group-containing substance in a target nucleic acid in a test sample using a capture probe which is complementary to the target nucleic acid, comprising:
- i) hybridizing the capture probe with the target nucleic acid;
- ii) reacting a compound of the formula 1
- R.sup.1 --CO--R.sup.2 ( 1)
- with an adenyl group in the hybridized target nucleic acid obtained in step 1, in the presence of an acid catalyst, to obtain a chemiluminescent substance;
- iii) qualitatively or quantitatively measuring the target nucleic acid by using a luminescent intensity of said chemiluminescent substance as an index; wherein:
- R.sup.1 is a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an aryl group having 1 to 18 carbon atoms or an aromatic heterocyclic group having 1 to 18 carbon atoms;
- wherein said R.sup.1 may be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group; and
- the group itself which substitutes or ring-condenses the R.sup.1 may be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group;
- and wherein
- R.sup.2 is an aldehyde group or a group represented by --CH(OR.sup.3)(OR.sup.4) in which R.sup.3 and R.sup.4 are the same or different groups which may form a ring by their partial binding and are selected from a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, and an aryl group having 1 to 18 carbon atoms;
- wherein said R.sup.3 and R.sup.4 can be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group; and
- the group itself which substitutes or ring-condenses the R.sup.3 and R.sup.4 groups can be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group.
- 15. The method of claim 14, wherein said target nucleic acid is first amplified by a polymerase chain reaction.
- 16. The method of claim 14, which further comprises a step (iia) of contacting the chemiluminescent substance obtained in step (ii) with a hydroxide solution initiator.
- 17. The method of claim 14, wherein said contacting step (iia) is performed in a polar solvent selected from the group consisting of dimethylformamide, isopropanol, acetonitrile, dioxane, dimethyl sulfoxide and water.
- 18. A method for measuring an adenyl group-containing substance in a target nucleic acid comprising the steps of:
- i) amplifying the target nucleic acid by polymerase chain reaction,
- ii) reacting the compound of the formula 1
- R.sup.1 --CO--R.sup.2 ( 1)
- with the adenyl group in the target nucleic acid amplified in step (i) to derive a chemiluminescent substance,
- (iii) qualitatively or quantitatively measuring the target nucleic acid by using a luminescent intensity of said chemiluminescent substance as an index wherein:
- R.sup.1 is a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an aryl group having 1 to 18 carbon atoms or an aromatic heterocyclic group having 1 to 18 carbon atoms;
- wherein said R.sup.1 may be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group; and
- the group itself which substitutes or ring-condenses the R.sup.1 may be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group; a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group;
- and wherein
- R.sup.2 is an aldehyde group or a group represented by --CH(OR.sup.3)(OR.sup.4) in which R.sup.3 and R.sup.4 are the same or different groups which may form a ring by their partial binding and are selected from a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, and an aryl group having 1 to 18 carbon atoms;
- wherein said R.sup.3 and R.sup.4 can be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group; and
- the group itself which substitutes or ring-condenses the R.sup.3 and R.sup.4 groups can be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group.
- 19. The method of claim 18, which further comprises a step (iia) of contacting the chemiluminescent substance obtained in step (i) with a hydroxide solution initiator.
- 20. The method of claim 18, wherein said contacting step (iia) is performed in a polar solvent selected from the group consisting of dimethylformamide, isopropanol, acetonitrile, dioxane, dimethyl sulfoxide and water.
- 21. A method for detecting or quantitating a substance in a test sample comprising:
- i) labeling an antigen or antibody with an adenyl group-containing substance or a nucleic acid containing adenine to obtain an adenine-labelled antigen or antibody;
- ii) reacting the adenine-labelled antigen or antibody obtained in step (i) with the substance to be measured, to form an adenine-labelled complex;
- iii) reacting a compound of the formula 1
- R.sup.1 --CO--R.sup.2 ( 1)
- with the adenine-labeled complex obtained in step (ii), in the presence of an acid catalyst, to derive a chemiluminescent substance, wherein;
- R.sup.1 is a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an aryl group having 1 to 18 carbon atoms or an aromatic heterocyclic group having 1 to 18 carbon atoms;
- wherein said R.sup.1 may be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group; and
- the group itself which substitutes or ring-condenses the R.sup.1 may be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group;
- and wherein
- R.sup.2 is an aldehyde group or a group represented by --CH(OR.sup.3)(OR.sup.4) in which R.sup.3 and R.sup.4 are the same or different groups which may form a ring by their partial binding and are selected from a hydrogen atom, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, and an aryl group having 1 to 18 carbon atoms;
- wherein said R.sup.3 and R.sup.4 can be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group; and
- the group itself which substitutes or ring-condenses the R.sup.3 and R.sup.4 groups can be substituted or ring-condensed with at least one group selected from the group consisting of a carboxyl group, hydroxyl group, amino group, amide group, sulfonamide group, sulfide group, sulfoxide group, sulfone group, nitro group, a halide atom, mercapto group, carbonyl group, azide group, an alkylamino group having 1 to 12 carbon atoms, an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 1 to 12 carbon atoms, an alkynyl group having 1 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, a polyalkoxy group, an aryl group, an aryloxy group, and a heterocyclic group;
- and
- iv) qualitatively or quantitatively measuring the substance to be measured by a luminescent intensity from the chemiluminescent substance obtained in step (iii) as an index.
- 22. The method of claim 21, wherein said adenine-containing labelling substance is a nucleic acid and further comprising a step (iia) in which said nucleic acid is amplified by a polymerase chain reaction.
- 23. The method of claim 21, which further comprises a step (iiia) of contacting said chemilumiscent substance obtained in step (iii) with a hydroxide solution initiator.
- 24. The method of claim 21, wherein said contacting step (iiia) is performed in a polar solvent selected from the group consisting of dimethylformamide, isopropanol, acetonitrile, dioxane, dimethyl sulfoxide and water.
Priority Claims (2)
| Number |
Date |
Country |
Kind |
| 5-062631 |
Feb 1993 |
JPX |
|
| 5-067906 |
Mar 1993 |
JPX |
|
Parent Case Info
This application is a continuation of application Ser. No. 08/109,721 filed on Aug. 19, 1993, now abandoned.
US Referenced Citations (1)
| Number |
Name |
Date |
Kind |
| 4828979 |
Klevan et al. |
May 1989 |
|
Continuations (1)
|
Number |
Date |
Country |
| Parent |
109721 |
Aug 1993 |
|
Patent Grant
5744307
