Organotellurium compounds, compositions and methods of use thereof

Patent metadata

Field	Value
Publication number	US-12135325-B2
Application number	US-202017024913-A
Country	US
Kind code	B2
Filing date	Sep 18, 2020
Priority date	Aug 20, 2014
Publication date	Nov 5, 2024
Grant date	Nov 5, 2024

Abstract

A compound of formula (I):as described herein and methods and uses thereof as for mass tagging a biosensor or biologically active material.

First claim

The invention claimed is:

1. A kit capable of mass detection assay, the kit comprising:
a plurality of mass tags, each mass tag comprising a tellurophene compound of the below formula (I);

wherein
A is a naturally occurring isotope of Te;
R 1 is selected from H, unsubstituted or substituted C 1 -C 20 alkyl, unsubstituted or substituted C 3 -C 20 cycloalkyl, unsubstituted or substituted aryl and an electron withdrawing group;
L is C 1 - 30 alkylene, unsubstituted or substituted with one or more substituents, and/or optionally interrupted with one or more heteromoieties independently selected from O, S, NR 7 , and/or optionally interrupted with one or more of C(O) and C(S);
R 7 is independently selected from H, PG and C 1-6 alkyl;
X is a reactive functional group selected from halo, OH, Ots, Oms, C(O)H, C(O)OR 8 , C(O)NR 9 R 10 , O—C(O)—OR 11 , O—C(O)—NR 12 , C(O)ONR 13 R 14 , C(O)R 15 , C(O)SR 16 , NR 17 R 18 , or a maleimide,
R 8 is selected from H, C 1-6 alkyl, aryl and C 1-6 alkylenearyl, wherein the latter three groups are unsubstituted or substituted with one or more of halo and NO 2 ;
R 9 and R 10 are independently selected from H, C 1-6 alkyl, aryl and C 1-6 alkylenearyl, wherein the latter three groups are unsubstituted or substituted with one or more of halo and NO 2 , or
R 9 and R 10 , together with the N atom to which they are bonded, form a 4 to 12 membered monocyclic or bicyclic, saturated or unsaturated ring unsubstituted or substituted with one or more ═O, ═S, halo and C 1-6 alkyl;
R 11 is selected from C 1-6 alkyl, aryl and C 1-6 alkylenearyl, wherein the latter three groups are unsubstituted or substituted with one or more of halo and NO 2 ;
R 12 is selected from C 1-6 alkyl, aryl and C 1-6 alkylenearyl, wherein the latter three groups are unsubstituted or substituted with one or more of halo and NO 2 ;
R 13 and R 14 are independently selected from H, C 1-6 alkyl, aryl and C 1-6 alkylenearyl, wherein the latter three groups are unsubstituted or substituted with one or more of halo and NO 2 , or
R 13 and R 14 , together with the N atom to which they are bonded, form a 4 to 12 membered monocyclic or bicyclic, saturated or unsaturated ring unsubstituted or substituted with one or more ═O, ═S, halo and C 1-6 alkyl;
R 15 is halo;
R 16 is selected from C 1-6 alkyl, aryl and C 1-6 alkylenearyl, wherein the latter three groups are unsubstituted or substituted with one or more of halo and NO 2 ;
R 17 and R 18 are independently selected from H, C(O)C 1-6 alkyl, C 1-6 alkyl, aryl and C 1-6 alkylenearyl, wherein the latter three groups are unsubstituted or substituted with one or more of halo and NO 2 , or R 17 and R 18 , together with the N atom to which they are bonded, form a 4 to 12 membered monocyclic or bicyclic, saturated or unsaturated ring unsubstituted or substituted with one or more ═O, ═S, halo and C 1-6 alkyl; and
one or more available hydrogens are optionally replaced with D;
or a salt and/or solvate thereof;
with proviso that when X is C(O)OR 19 and R 19 is H or C 1-6 alkyl, L is not C 1-8 alkylene; and
when X is OH, L is not C 1-2 alkylene; and
wherein each mass tag comprises a distinct tellurium isotope.

2. The kit of claim 1 , wherein each mass tag is conjugated to a biologically active material, wherein the biologically active material is selected from affinity reagent, polypeptide, nucleic acid, peptidic nucleic acid, oligosaccharide, polysaccharide lipopolysaccharide, hormone, pharmacologically active substance, steroid, vitamin, amino acid and sugar.

3. A method of detecting or quantifying a plurality of target analytes by mass cytometry comprising the steps of:
a. providing a cell or cell population;
b. providing a plurality of tellurophene mass tagged biologically active materials, each comprising a mass tag as defined in claim 1 and a biologically active material, wherein the biologically active material specifically binds or reacts with one of the plurality of target analytes;
c. mixing the cell or cell population with the plurality of tellurophene mass tagged biologically active materials; and
d. detecting tellurium labelling and/or quantitating the amount of tellurium labelling of the cell or cell population by mass cytometry;
wherein each of the tellurophene mass tagged biologically active materials comprises a distinct tellurium isotope;
wherein the biologically active material is selected from affinity reagent, polypeptide, nucleic acid, peptidic nucleic acid, oligosaccharide, polysaccharide lipopolysaccharide, hormone, pharmacologically active substance, steroid, vitamin, amino acid and sugar, optionally the affinity reagent is selected from a polypeptide affinity reagent, aptamer, nucleic acid or lectin.

4. The method of claim 3 , wherein the mass cytometry comprises analysis of a single cell.

5. The method of claim 3 , wherein the mass cytometry comprises vaporizing the cell population and analyzing the cell population by time of flight mass spectrometry.

6. The method of claim 3 , wherein the mass cytometry comprises subjecting the cell or cell population to laser ablation.

7. The method of claims 3 , wherein the affinity reagent is the polypeptide affinity reagent.

8. The method of claim 7 , wherein polypeptide affinity reagent is an antibody.

9. The method of claim 3 , wherein the biologically active material is a polynucleotide probe.

10. The method of claim 7 , wherein the polypeptide affinity reagent is a streptavidin reagent or an avidin reagent.

11. The method of claim 3 , wherein the biologically active material is tagged with the mass tag through a polymeric backbone.

12. The kit of claim 2 , wherein the mass tag is conjugated to a free amine of the biologically active material.

13. The kit of claim 2 , wherein the mass tag is conjugated to a thiol of the biologically active material.

14. The kit of claim 2 , wherein the affinity reagent is selected from a polypeptide affinity reagent, aptamer, nucleic acid or lectin.

15. The kit of claim 14 , wherein the affinity reagent is the polypeptide affinity reagent.

16. The kit of claim 15 , wherein the polypeptide affinity reagent is an antibody or a binding fragment thereof.

17. The kit of claim 15 , wherein the polypeptide affinity reagent is an avidin reagent, optionally a streptavidin reagent.

18. The kit of claim 14 , wherein the nucleic acid is a polynucleotide probe.

19. The kit of claim 2 , wherein each of the plurality of mass tags is distinguishable from any other tellurophene mass tag.

20. The kit of claim 2 , wherein one or more of the plurality of mass tags is conjugated to the biologically active material through a polymeric backbone.

21. The kit of claim 1 , wherein the plurality of mass tags are packaged as barcoding reagents.

Assignees

• Governing Council Univ Toronto
• Univ Health Network

Inventors

• Nitz Mark
• Edgar Landon J
• Wouters Bradly G
• Hedley David
• Willis Lisa M
• Lumba Matthew A
• Park Hanuel
• Vellanki Ravi N

Classifications

• G01N2560/00

  Chemical aspects of mass spectrometric analysis of biological material · CPC title

• G01N2458/15

  Non-radioactive isotope labels, e.g. for detection by mass spectrometry · CPC title

• G01N33/569

  for microorganisms, e.g. protozoa, bacteria, viruses · CPC title

• C07H15/04

  attached to an oxygen atom of the saccharide radical · CPC title

• C07D345/00

  Heterocyclic compounds containing rings having selenium or tellurium atoms as the only ring hetero atoms · CPC title