Labeled transition metal complexes

• US 9,188,590 B2
• Filed: 12/01/2005
• Issued: 11/17/2015
• Est. Priority Date: 12/08/2004
• Status: Active Grant

• Current Assignee: Leica Biosystems Newcastle Ltd. (Danaher Corporation)
• Original Assignee: Leica Biosystems Newcastle Ltd. (Danaher Corporation)
• Inventors: Lacombe, Marie, Talman, Eduard Gerhard, Veuskens, Jacky Theo Maria, Opdam, Franciscus Johannes
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): SAMALA, JAGADISHWAR RAO
• Application Number:
  US11/721,189
• Publication Number:
  US 20100155590A1
• Time in Patent Office: 3,638 Days
• Field of Search: 514/188, 514/212.01, 530/300, 530/395, 436/84, 436/546, 536/23.1, 536/24.3, 536/26.6
• US Class Current: 1/1
• CPC Class Codes: C07F 15/0093 without a metal-carbon linkage
• CPC Class Codes: G01N 33/58 involving labelled substances G01N33/53 takes precedence

Abstract

The invention relates to a labeled transition metal complex comprising a transition metal atom, a reactive moiety for allowing a chemical or biological entity to become attached to the transition metal atom, an inert tridentate moiety as a stabilizing bridge, and a marker. The invention also relates to a labeled chemical or biological entity comprising a chemical or biological entity which is attached to said labeled transition metal complex, to the use of said complex for creating a defined shift in the molecular mass of said entity in order to facilitate mass spectrometric analysis of said entity, to methods for rendering chemical or biological entities distinguishable by mass spectrometry as well as to methods for mass spectrometric analysis of the chemical or biological entities. In addition, the present invention also relates to a set of at least two of said transition metal complexes of different molecular mass, to transition metal complexes comprising different stable isotopes, to chemical or biological entities obtained by a method of the invention and to a kit of parts supporting the use and/or methods of the invention.

Claims

1. A labeled transition metal complex comprising a transition metal atom, a reactive moiety for allowing a chemical or biological entity to become attached to the transition metal atom, an inert tridentate moiety as a stabilizing bridge, and a marker, wherein the transition metal is chosen from the group consisting of vanadium, chromium, iron, ruthenium, palladium, platinum, molybdenum, tungsten, cobalt, manganese, osmium, rhodium, iridium, zinc, and cadmium;

wherein the marker is separated from the tridentate moiety by means of a spacer, wherein the spacer comprises a chain having between 4 and 20 atoms selected from carbon, nitrogen, and oxygen.

2. A complex according to claim 1, wherein the transition metal is chosen from the group consisting of iron, nickel, ruthenium, palladium, platinum, molybdenum, tungsten, and cobalt.

3. A complex according to claim 2, wherein the transition metal is platinum, cobalt, or ruthenium.

4. A complex according to of claim 1, wherein the transition metal atom is attached to the tridentate moiety by means of three donor atoms, each being independently selected from the group of nitrogen, oxygen, sulphur, and phosphorus atoms, which donor atoms are present in the tridentate moiety.

5. A complex according to claim 4, wherein the transition metal atom is attached to the tridentate moiety by means of three nitrogen atoms.

6. A complex according to claim 4, wherein the donor atoms in the tridentate moiety are separated from each other by 1 to 5, preferably 1 to 3 atoms.

7. A complex according to claim 1, wherein the marker is a fluorescent label.

8. A complex according to claim 1, wherein the reactive moiety is chosen from the group consisting of Cl⁻

, NO₃⁻

, HCO₃⁻

, CO₃²⁻

, SO₃²⁻

, ZSO³⁻

, I⁻

, Br⁻

, F⁻

, acetate, carboxylate, phosphate, ethylnitrate, oxalate, citrate, a phosphonate, ZO⁻

, and water wherein Z represents a hydrogen moiety or an alkyl or aryl group having from 1 to 10 carbon atoms.

9. A labeled chemical or biological entity comprising a chemical or biological entity which is attached to a transition metal complex as defined in claim 1, wherein the chemical or biological entity has replaced the reactive moiety.

10. A labeled chemical or biological entity according to claim 9, wherein the entity is selected from the group consisting of amino acids, peptides, oligopeptide, polypeptides, proteins, immunoglobulins, enzymes, synzymes, phospholipides, glycoproteins, nucleic acids, nucleosides, nucleotides, oligonucleotides, polynucleotides, peptide nucleic acids, peptide nucleic acid oligomers, peptide nucleic acid polymers, amines and aminoglycosides.

11. A set of at least two transition metal complexes of different molecular weight, wherein each of said transition metal complexes is as defined in claim 1.