Release tag compounds producing ketone signal groups

• US 5,610,020 A
• Filed: 02/08/1996
• Issued: 03/11/1997
• Est. Priority Date: 02/01/1982
• Status: Expired due to Fees

• Current Assignee: Northeastern University
• Original Assignee: Northeastern University
• Inventors: Giese, Roger W., Abdel-Baky, Samy, Xu, Linxiao
• Primary Examiner(s): Killos, Paul J.
• Application Number:
  US08/598,439
• Time in Patent Office: 397 Days
• Field of Search: 435/7.1, 435/7.2, 435/6, 435/175, 435/183
• US Class Current: 435/7.1
• CPC Class Codes: C07D 207/46 with hetero atoms directly attached to the ring nitrogen atom
• CPC Class Codes: G01N 33/532 Production of labelled immunochemicals
• CPC Class Codes: G01N 33/582 with fluorescent label
• CPC Class Codes: G01N 33/78 Thyroid gland hormones , e.g. T3, T4, TBH, TBG or their receptors

Abstract

A release tag reagent suitable for use in the chemical analysis of a substance to be detected comprises signal, release, and reactivity groups. A class of release tag compounds that are cleaved to release as signal groups very stable electrophoric ketones which are sufficiently volatile for determination in the gas phase of an analytical reaction mixture is disclosed.

Claims

1. In an assay which includes contacting an analyte-containing sample with a labeled reagent, or with a conjugate made by covalently reacting a labeled reagent with standard said analyte, or with an analog of, ligand for, or specific binding partner of said analyte, incubating said contacted sample, and measuring the amount of label, the improvement which comprises:

using as the labeled reagent a release tag compound, S-Re-Rx, wherein S is a signal group covalently bound to group Re, and Re is a cleavable release group which is covalently bound to group Rx which is a reactivity group;

and S is further defined as comprising a halogenated electron-absorbing group which can be measured by electron capture detection;

and Re is further defined as comprising a functionality selected from the group consisting of α

-hydroxyketos and β

-hydroxyketos, and is capable of releasing the signal group in a volatile form suitable for measuring by electron capture detection;

and Rx is further defined as comprising a functional group which is capable of forming a covalent bond with another molecule.

7. The assay of claim 1 wherein Re is an α

,β

-dihydroxyketo group.

8. The assay of claim 1 wherein said signal group is released as a ketone compound.

9. The assay of claim 1 wherein said signal group is released as a polyfluorinated ketone compound.

2. In an assay which includes contacting an analyte-containing sample with a labeled reagent, or with a conjugate made by covalently reacting a labeled reagent with standard said analyte, or with an analog of ligand for, or specific binding partner of said analyte, incubating said contacted sample, and measuring the amount of label, the improvement which comprises:

using as the labeled reagent a release tag compound, S-Re-Rx, wherein S is a signal group covalently bound to group Re, and Re is a cleavable release group which is covalently bound to group Rx which is a reactivity group;

and S is further defined as comprising a halogenated electron-absorbing group which can be measured by electron capture detection;

and Re is further defined as comprising a functionality cleavable by heat and is capable of releasing the signal group in a volatile form suitable for measuring in the gas phase;

and Rx is further defined as comprising a functional group which is capable of forming a covalent bond with another molecule;

said improvement further comprising measuring the amount of label following thermal release of the signal group.

3. The assay of claim 2 wherein Re is a β

-hydroxyketo group.

4. The assay of claim 2 wherein Re is an α

,β

-dihydroxyketo group.

5. The assay of claim 2 wherein said signal group is released as a ketone compound.

6. The assay of claim 2 wherein said signal group is released as a polyfluorinated ketone compound.