CA2478979A1 - Detection of glucose in solutions also containing an alpha-hydroxy acid or a beta-diketone - Google Patents

Detection of glucose in solutions also containing an alpha-hydroxy acid or a beta-diketone Download PDF

Info

Publication number
CA2478979A1
CA2478979A1 CA002478979A CA2478979A CA2478979A1 CA 2478979 A1 CA2478979 A1 CA 2478979A1 CA 002478979 A CA002478979 A CA 002478979A CA 2478979 A CA2478979 A CA 2478979A CA 2478979 A1 CA2478979 A1 CA 2478979A1
Authority
CA
Canada
Prior art keywords
methyl
boronobenzyl
anthracene
benzyl
compound
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CA002478979A
Other languages
French (fr)
Other versions
CA2478979C (en
Inventor
George Y. Daniloff
Aristotle G. Kalivretenos
Alexandre V. Nikolaitchik
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sensors for Medicine and Science Inc
Original Assignee
Individual
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Individual filed Critical Individual
Publication of CA2478979A1 publication Critical patent/CA2478979A1/en
Application granted granted Critical
Publication of CA2478979C publication Critical patent/CA2478979C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/54—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving glucose or galactose
    • 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
    • G01N33/531—Production of immunochemical test materials
    • G01N33/532—Production of labelled immunochemicals
    • G01N33/533—Production of labelled immunochemicals with fluorescent label
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds
    • 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
    • G01N33/536—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase
    • G01N33/542—Immunoassay; Biospecific binding assay; Materials therefor with immune complex formed in liquid phase with steric inhibition or signal modification, e.g. fluorescent quenching
    • 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
    • G01N33/58—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances
    • G01N33/582—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances with fluorescent label
    • 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
    • G01N33/66—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood sugars, e.g. galactose
    • 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
    • Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
    • Y10T436/142222—Hetero-O [e.g., ascorbic acid, etc.]
    • Y10T436/143333—Saccharide [e.g., DNA, etc.]
    • Y10T436/144444—Glucose

Abstract

Compositions and methods for determining the presence or concentration of glucose in a sample which may also contain an alpha-hydroxy acid or a beta-diketone. The method uses a compound having at least two recognition elements for glucose, oriented such that the interaction between the compound and glucose is more stable than the interaction between the compound and the alpha-hydroxy acid or beta-diketone, such that the presence of the alpha-hydroxy acid or the beta-diketone does not substantially interfere with said determination.

Claims (34)

1. A method for detecting the presence or concentration of glucose in a sample which may also contain an alpha-hydroxy acid or a beta-diketone, which comprises:
a) exposing the sample to a compound having at least two recognition elements for glucose, oriented such that the interaction between the compound and glucose is more stable than the interaction between the compound and the alpha-hydroxy acid or beta-diketone, said compound also containing a detectable moiety having a detectable quality that changes in a concentration-dependent manner when said compound is exposed to glucose in said sample;
and b) measuring any change in said detectable quality to thereby determine the presence or concentration of glucose in said sample, wherein the presence of the alpha-hydroxy acid or the beta-diketone does not substantially interfere with said determination.
2. The method of claim 1, wherein the compound has the following structure:
wherein:
-R1 and R2 are the same or different and are selected from the following: i) hydrogen; ii) a substituent to modify the pKa and hydrolytic stability of the R8 moiety, iii) a detectable moiety, or iv) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-R3 is hydrogen or a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-R4 and R5 are the same or different and are selected from the following: i) hydrogen, ii) a substituent to modify the pKa and hydrolytic stability of the R8 moiety, iii) a detectable moiety, or iv) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-each Z is independently carbon or nitrogen;
-R6 and R7 are the same or different and are i) linking groups having from zero to ten contiguous or branched carbon and/or heteroatoms, or ii) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-R is selected from the following: i) an aliphatic and/or aromatic spacer containing from 1 to 10 contiguous atoms selected from the group consisting of carbon, oxygen, nitrogen, sulfur and phosphorus, ii) a detectable moiety, or iii) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-each R8 is the same or different and is a moiety capable of interaction with the vicinal diol groups present in glucose; and -R9 and R10 are the same or different, and are i) hydrogen, ii) a detectable moiety, iii) a group which is a) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety, and/or b) includes a functional group capable of altering the physical properties of the compound;
with the proviso that the indicator compound contains at least one detectable moiety associated therewith.
3. The method of claim 2, wherein R8 is selected from the group consisting of boronic acid, boronate ion, arsenious acid, arsenite ion, telluric acid, tellurate ion, germanic acid, germanate ion, and combinations thereof.
4. The method of claim 3, wherein each R8 is a boronic acid group.
5. The method of claim 2, wherein the compound comprises at least two detectable moieties that are capable of energy transport from one to the other, and wherein said energy transport is modulated by the presence of glucose in the sample.
6. The method of claim 2, wherein at least one of R, R1, R2, R4, R5, R9 or R10 comprises a fluorophore moiety and further wherein at least one of those groups comprises a quenching moiety, and wherein said fluorophore is either quenched or dequenched when said compound interacts with glucose in the sample.
7. The method of claim 2, wherein the compound comprises a fluorophore, and the fluorescence of said fluorophore is modulated by the interaction of said compound with glucose.
8. The method of claim 1, wherein the sample is a physiological fluid.
9. The method of claim 8, wherein the physiological fluid is selected from the group consisting of blood, plasma, serum, interstitial fluid, cerebrospinal fluid, urine, saliva, intraocular fluid, lymph, tears, sweat, and physiological buffers.
10. The method of claim 1, wherein the compound is exposed to the sample in solution.
11. The method of claim 1, wherein the compound is immobilized on or within a solid support.
12. The method of claim 11, wherein the solid support is a polymeric matrix.
13. The method of claim 1, wherein the compound is associated with an implantable device, and wherein step a) takes place in vivo.
14. The method of claim 2, wherein R is an anthracene residue; R1, R2, R3, R4 and R5 are hydrogen; R6 and R7 are dimethylamine residues; each R8 is a boronic acid group; one or both of R9 and R10 are aliphatic carboxylic acid residues; and each Z is carbon.
15. The method of claim 14, wherein one or both of R9 and R10 are propionic acid residues.
16. The method of claim 2, wherein R is a hexamethylene residue; R1, R2, R3, R4 and R5 are hydrogen;
R6 and R7 are dimethylamine residues; each R8 is a boronic acid group; R9 is a naphthalimide residue; R10 is a dimethylaminobenzyl residue; and each Z is carbon.
17. The method of claim 2, wherein R is an anthracene residue; R1, R2, R3, R4 and R5 are hydrogen; R6 and R7 are dimethylamine residues; each R8 is a boronic acid group; R9 and R10 are the same or different and are selected from the group consisting of a methacrylamidoalkyl residue, a methacroyloxyethoxyalkyl residue, a hydroxyethoxyalkyl residue, and an aminoalkyl residue; and each Z is carbon.
18. The method of claim 2, wherein the compound is selected from the group consisting of:
9-[N-(2-boronobenzyl)-N-[2-(2-methacroyloxyethoxy)-ethylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(2-hydroxyethoxy)ethylamino]methyl)anthracene;
9,10-bis[N-(2-boronobenzyl)-N-[2-(carboxyethyl)amino]-methyl]anthracene;
9,10-bis[N-(2-boronobenzyl)-N-[3-(methacrylamido)-propylamino]methylanthracene;
9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)-propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(2-hydroxyethoxy)ethylamino]methyl]anthracene;
9,10-bis[N-(2-boronobenzyl)-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]anthracene;
9,10-bis[N-(2-boronobenzyl)-N-[5-aminopentylamino]-methyl]anthracene; and 9-[N-(2-boronobenzyl)-N-[3-(methacrylamido) propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[6-(cyclohexanecarboxamido)hexylamino]methyl]anthracene;

-83-~

9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(carboxyethyl)amino]methyl]anthracene;
9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[3-(N-6-(9-anthracenecarboxamido)hexylamino carbonyl)ethylamino]methyl]anthracene;
9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[6-(3-carboxypropionamido)hexylamino]methyl]anthracene;
N-(3-Methacrylamidopropyl)-4-[2-N-[[2-(borono)benzyl]-[6-(N-[2-(borono)benzyl]-6-N-(3-carboxypropanamidoethyl)aminohexyl]]aminoethylamino]napht halene-1,8-dicarboximide;
N-Butyl-4-[2-N-[[2-(borono)benzyl]-[6-(N-[2-(borono)benzyl]-6-N-(2-methacrylamidoethyl)aminohexyl]]aminoethylamino]naphthale ne-1,8-dicarboximide; and salts thereof.
19. A compound having the following structure wherein:

-R1 and R2 are the same or different and are selected from the following: i) hydrogen; ii) a substituent to modify the pKa and hydrolytic stability of the R8 moiety, iii) a detectable moiety, or iv) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-R3 is hydrogen or a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-R9 and R5 are the same or different and are selected from the following: i) hydrogen, ii) a substituent to modify the pKa and hydrolytic stability of the R8 moiety, iii) a detectable moiety, or iv) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-each Z is independently carbon or nitrogen;
-R6 and R7 are the same or different and are i) linking groups having from zero to ten contiguous or branched carbon and/or heteroatoms, or ii) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-R is selected from the following: i) an aliphatic and/or aromatic spacer containing from 1 to 10 contiguous atoms selected from the group consisting of carbon, oxygen, nitrogen, sulfur and phosphorus, ii) a detectable moiety, or iii) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-each R8 is the same or different and is an optionally protected moiety which when unprotected is capable of interaction with the vicinal diol groups present in glucose; and -R9 and R10 are the same or different, and are i) hydrogen, ii) a detectable moiety, iii) a group which is a) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety, and/or b) includes a functional group capable of altering the physical properties of the compound;
with the proviso that the indicator compound contains at least one detectable moiety associated therewith.
20. The compound of claim 19, wherein R8 is selected from the group consisting of boronic acid, boronate ion, arsenious acid, arsenite ion, telluric acid, tellurate ion, germanic acid, germanate ion, all optionally protected, and combinations thereof.
21. The compound of claim 20, wherein each R8 is an optionally protected boronic acid group.
22. The compound of claim 19, wherein the compound comprises a fluorophore, and the fluorescence of said fluorophore is modulated by the interaction of said compound with glucose.
23. The compound of claim 19, wherein R is an anthracene residue; R1, R2, R3, R4 and R5 are hydrogen; R6 and R7 are dimethylamine residues; each R8 is an optionally protected boronic acid group; one or both of R9 and R10 are aliphatic carboxylic acid residues; and each Z
is carbon.
24. The compound of claim 23, wherein one or both of R9 and R10 are propionic acid residues.
25. The compound of claim 1, wherein R is an anthracene residue; R1, R2, R3, R4 and R5 are hydrogen; R6 and R7 are dimethylamine residues; each R8 is an optionally protected boronic acid group; R9 and R10 are the same or different and are selected from the group consisting of a methacrylamidoalkyl residue, a methacroyloxyethoxyalkyl residue, a hydroxyethoxyalkyl residue, and an aminoalkyl residue; and each Z is carbon.
26. The compound of claim 19, wherein the compound is selected from the group consisting of:
9-[N-[2-(5,5-dimethylborinan-2-yl)benzyl]-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]-10-[N-[2-(5,5-dimethylborinan-2-yl)benzyl]-N-[2-(2-hydroxyethoxy)ethylamino]-methyl]anthracene;
9-[N-(2-boronobenzyl)-N-[2-(2-methacroyloxyethoxy)-ethylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(2-hydroxyethoxy)ethylamino]methyl]anthracene;
9,10-bis[N-(2-boronobenzyl)-N-[2-(carboxyethyl)amino]-methyl]anthracene;
9,10-bis[N-[2-(5,5-dimethylborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]methylanthracene;
9,10-bis[N-(2-boronobenzyl)-N-[3-(methacrylamido)-propylamino]methylanthracene;
9-[N-[2-(5,5-dimethylborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N-[2-(5,5-dimethylborinan-2-yl)benzyl]-N-[2-(2-hydroxyethoxy)-ethylamino]methyl]anthracene;
9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)-propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(2-hydroxyethoxy)ethylamino]methyl]anthracene;

9,10-bis[N-[2-(5,5-dimethylborinan-2-yl)benzyl]-N-[2-(2-methacroyloxyethoxy)ethylamino)methyl]anthracene;
9,10-bis(N-(2-boronobenzyl)-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]anthracene;
9,10-bis[N-(2-boronobenzyl)-N-[5-aminopentylamino]-methyl]anthracene;
9-[N-(2-boronobenzyl)-N-[3-(methacrylamido) propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[6-(cyclohexanecarboxamido)hexylamino]methyl]anthracene;
9-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]N-[3-(methacrylamido)propylamino]methyl]-10-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[6-(cyclohexanecarboxamido)hexylamino]methyl]anthracene;
9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(carboxyethyl)amino]methyl]anthracene;
9-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[2-(carboxyethyl)amino]methyl]anthracene;
9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[3-(N-6-(9-anthracenecarboxamido)hexylamino carbonyl)ethylamino]methyl]anthracene;
9-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[3-(N-6-(9-anthracenecarboxamido)hexylamino carbonylethylaminomethyl]anthracene;
9-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[6-(3-carboxypropionamido)hexylamino]methyl]anthracene;
9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-baronobenzyl)-N-[6-(3-carboxypropionamido)hexylamino]methyl]anthracene;
N-(3-Methacrylamidopropyl)-4-[2-N-[[2-(borono)benzyl]-[6-(N-[2-(borono)benzyl]-6-N-(3-carboxypropanamidoethyl)aminohexyl]]aminoethylamino]napht halene-1,8-dicarboximide;
N-Butyl-4-[2-N-[[2-(borono)benzyl]-[6-(N-[2-(borono)benzyl]-6-N-(2-methacrylamidoethyl)aminohexyl]]aminoethylamino]naphthale ne-1,8-dicarboximide; and salts thereof.
27. A detection system for detecting the presence or concentration of glucose in a sample which may also contain an alpha-hydroxy acid or a beta-diketone, which comprises a compound having the following structure wherein:

-R1 and R2 are the same or different and are selected from the following: i) hydrogen; ii) a substituent to modify the pKa and hydrolytic stability of the R8 moiety, iii) a detectable moiety, or iv) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-R3 is hydrogen or a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-R4 and R5 are the same or different and are selected from the following: i) hydrogen, ii) a substituent to modify the pKa and hydrolytic stability of the R8 moiety, iii) a detectable moiety, or iv) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-each Z is independently carbon or nitrogen;
-R6 and R7 are the same or different and are i) linking groups having from zero to ten contiguous or branched carbon and/or heteroatoms, or ii) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-R is selected from the following: i) an aliphatic and/or aromatic spacer containing from 1 to 10 contiguous atoms selected from the group consisting of carbon, oxygen, nitrogen, sulfur and phosphorus, ii) a detectable moiety, or iii) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety;
-each R8 is the same or different and is an optionally protected moiety which when unprotected is capable of interaction with the vicinal diol groups present in glucose; and -R9 and R10 are the same or different, and are i) hydrogen, ii) a detectable moiety, iii) a group which is a) a linking group capable of attachment to a solid support or a polymeric matrix, said support or matrix optionally containing a detectable moiety, and/or b) includes a functional group capable of altering the physical properties of the compound;
with the proviso that the indicator compound contains at least one detectable moiety associated therewith.
28. The detection system of claim 27, wherein R8 is selected from the group consisting of boronic acid, boronate ion, arsenious acid, arsenite ion, telluric acid, tellurate ion, germanic acid, germanate ion, all optionally protected, and combinations thereof.
29. The detection system of claim 28, wherein each R8 is an optionally protected boronic acid group.
30. The detection system of claim 27, wherein the compound comprises a fluorophore, and the fluorescence of said fluorophore is modulated by the interaction of said compound with glucose.
31. The detection system of claim 27, wherein R is an anthracene residue; R1, R2, R3, R4 and R5 are hydrogen;
R6 and R7 are dimethylamine residues; each R8 is an optionally protected boronic acid group; one or both of R9 and R10 are aliphatic carboxylic acid residues; and each Z
is carbon.
32. The detection system of claim 31, wherein one or both of R9 and R10 are propionic acid residues.
33. The detection system of claim 27, wherein R is an anthracene residue; R1, R2, R3, R4 and R5 are hydrogen;
R6 and R7 are dimethylamine residues; each R8 is a boronic acid group; R9 and R10 are the same or different and are selected from the group consisting of a methacrylamidoalkyl residue, a methacroyloxyethoxyalkyl residue, a hydroxyethoxyalkyl residue, and an aminoalkyl residue; and each Z is carbon.
34. The detection system of claim 27, wherein the compound is selected from the group consisting of:
9-[N-[2-(5,5-dimethylborinan-2-yl)benzyl]-N-[2-(2-methacroyloxyethoxy)ethylamino]methyll-10-[N-[2-(5,5-dimethylborinan-2-yl)benzyl]-N-[2-(2-hydroxyethoxy)ethylamino]-methyl]anthracene;
9-[N-(2-boronobenzyl)-N-[2-(2-methacroyloxyethoxy)-ethylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(2-hydroxyethoxy)ethylamino]methyl]anthracene;
9,10-bis[N-(2-boronobenzyl)-N-[2-(carboxyethyl)amino]-methyl]anthracene;
9,10-bis[N-[2-(5,5-dimethylborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]methylanthracene;
9,10-bis[N-(2-boronobenzyl)-N-[3-(methacrylamido)-propylamino]methylanthracene;
9-[N-[2-(5,5-dimethylborinan-2-yl)benzyl]-N-[3-(methacrylamido)propylamino]methyl)-10-[N-[2-(5,5-dirnethylborinan-2-yl)benzyl]-N-[2-(2-hydroxyethoxy)-ethylamino]methyl]anthracene;
9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)-propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(2-hydroxyethoxy)ethylamino]methyl]anthracene;

9,10-bis[N-[2-(5,5-dimethylborinan-2-yl)benzyl]-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]anthracene;
9, 10-bis [N-(2-boronobenzyl)-N-[2-(2-methacroyloxyethoxy)ethylamino]methyl]anthracene;
9,10-bis[N-(2-boronobenzyl)-N-[5-aminopentylamino]-methyl]anthracene; and 9- [N- (2-boronobenzyl) -N- [3- (methacrylamido) propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[6-(cyclohexanecarboxamido)hexylamino]methyl]anthracene;
9-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]N-[3-(methacrylamido)propylamino]methyl]-10-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[6-(cyclohexanecarboxamido)hexylamino]methyl]anthracene;
9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[2-(carboxyethyl)amino]methyl]anthracene;
9-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[2-(carboxyethyl)amino]methyl]anthracene;
9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[3-(N-6-(9-anthracenecarboxamido)hexylamino carbonyl)ethylamino]methyl]anthracene;
9-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[3-(N-6-(9-anthracenecarboxamido)hexylamino carbonylethylaminomethyl]anthracene;
9-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[3-(methacrylamido)propylamino]methyl]-10-[N-[2-(4,4,5,5,-tetramethyl-1,3,2-dioxaborolano)benzyl]-N-[6-(3-carboxypropionamido)hexylamino]methyl]anthracene;
9-[N-(2-boronobenzyl)-N-[3-(methacrylamido)propylamino]methyl]-10-[N-(2-boronobenzyl)-N-[6-(3-carboxypropionamido)hexylamino]methyl]anthracene;
N-(3-Methacrylamidopropyl)-4-[2-N-[[2-(borono)benzyl]-[6-(N-[2-(borono)benzyl]-6-N-(3-carboxypropanamidoethyl)aminohexyl]]aminoethylamino]napht halene-1,8-dicarboximide;
N-Butyl-4-[2-N-[[2-(borono)benzyl]-[6-(N-[2-(borono)benzyl]-6-N-(2-methacrylamidoethyl)aminohexyl]]aminoethylamino]naphthale ne-1,8-dicarboximide; and salts thereof.
CA2478979A 2002-03-14 2003-03-14 Detection of glucose in solutions also containing an alpha-hydroxy acid or a beta-diketone Expired - Fee Related CA2478979C (en)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US36388502P 2002-03-14 2002-03-14
US60/363,885 2002-03-14
US10/187,903 US6800451B2 (en) 2001-01-05 2002-07-03 Detection of glucose in solutions also containing an alpha-hydroxy acid or a beta-diketone
US10/187,903 2002-07-03
PCT/US2003/007938 WO2003078424A1 (en) 2002-03-14 2003-03-14 Detection of glucose in solutions also containing an alpha-hydroxy acid or a beta-diketone

Publications (2)

Publication Number Publication Date
CA2478979A1 true CA2478979A1 (en) 2003-09-25
CA2478979C CA2478979C (en) 2011-09-20

Family

ID=28044431

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2478979A Expired - Fee Related CA2478979C (en) 2002-03-14 2003-03-14 Detection of glucose in solutions also containing an alpha-hydroxy acid or a beta-diketone

Country Status (9)

Country Link
US (2) US6800451B2 (en)
EP (1) EP1490359B1 (en)
JP (1) JP4431398B2 (en)
KR (1) KR101012325B1 (en)
AU (1) AU2003220293B2 (en)
BR (1) BR0308412A (en)
CA (1) CA2478979C (en)
MX (1) MXPA04008931A (en)
WO (1) WO2003078424A1 (en)

Families Citing this family (81)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030211507A1 (en) * 1996-03-29 2003-11-13 Anson Hatch Microscale diffusion immunoassay in hydrogels
US8346337B2 (en) 1998-04-30 2013-01-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8974386B2 (en) 1998-04-30 2015-03-10 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8688188B2 (en) 1998-04-30 2014-04-01 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8480580B2 (en) 1998-04-30 2013-07-09 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US6949816B2 (en) 2003-04-21 2005-09-27 Motorola, Inc. Semiconductor component having first surface area for electrically coupling to a semiconductor chip and second surface area for electrically coupling to a substrate, and method of manufacturing same
US9066695B2 (en) 1998-04-30 2015-06-30 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US8465425B2 (en) 1998-04-30 2013-06-18 Abbott Diabetes Care Inc. Analyte monitoring device and methods of use
US6175752B1 (en) 1998-04-30 2001-01-16 Therasense, Inc. Analyte monitoring device and methods of use
US6664407B2 (en) * 2000-12-04 2003-12-16 Beckman Coulter, Inc. Electrochemical saccharide sensor
US6560471B1 (en) 2001-01-02 2003-05-06 Therasense, Inc. Analyte monitoring device and methods of use
US7041468B2 (en) 2001-04-02 2006-05-09 Therasense, Inc. Blood glucose tracking apparatus and methods
US20040106163A1 (en) * 2002-11-12 2004-06-03 Workman Jerome James Non-invasive measurement of analytes
AU2003287735A1 (en) * 2002-11-12 2004-06-03 Argose, Inc. Non-invasive measurement of analytes
US8771183B2 (en) 2004-02-17 2014-07-08 Abbott Diabetes Care Inc. Method and system for providing data communication in continuous glucose monitoring and management system
US7811231B2 (en) 2002-12-31 2010-10-12 Abbott Diabetes Care Inc. Continuous glucose monitoring system and methods of use
US8066639B2 (en) 2003-06-10 2011-11-29 Abbott Diabetes Care Inc. Glucose measuring device for use in personal area network
WO2005065241A2 (en) * 2003-12-24 2005-07-21 Argose, Inc. Smmr (small molecule metabolite reporters) for use as in vivo glucose biosensors
US7713745B2 (en) * 2004-04-13 2010-05-11 Sensors For Medicine And Science, Inc. Non-covalent immobilization of indicator molecules
JP4691333B2 (en) * 2004-07-23 2011-06-01 テルモ株式会社 Fluorescent monomer compound for saccharide measurement, fluorescent sensor substance for saccharide measurement, and saccharide measurement sensor for implantation in the body
DE602005000858T2 (en) * 2004-07-23 2008-01-17 Terumo K.K. Saccharide-measuring fluorescent monomer, saccharide-measuring fluorescent sensor substance and implantable saccharide-measuring sensor
JP4691345B2 (en) * 2004-10-07 2011-06-01 テルモ株式会社 Fluorescent monomer compound for saccharide measurement, fluorescent sensor substance for saccharide measurement, and saccharide measurement sensor for implantation in the body
US8112240B2 (en) 2005-04-29 2012-02-07 Abbott Diabetes Care Inc. Method and apparatus for providing leak detection in data monitoring and management systems
US7766829B2 (en) 2005-11-04 2010-08-03 Abbott Diabetes Care Inc. Method and system for providing basal profile modification in analyte monitoring and management systems
US8226891B2 (en) 2006-03-31 2012-07-24 Abbott Diabetes Care Inc. Analyte monitoring devices and methods therefor
US7620438B2 (en) 2006-03-31 2009-11-17 Abbott Diabetes Care Inc. Method and system for powering an electronic device
US8126554B2 (en) 2006-05-17 2012-02-28 Cardiac Pacemakers, Inc. Implantable medical device with chemical sensor and related methods
WO2007143225A2 (en) 2006-06-07 2007-12-13 Abbott Diabetes Care, Inc. Analyte monitoring system and method
EP2054476B9 (en) * 2006-07-25 2012-03-14 Glumetrics, Inc. Flourescent dyes for use in glucose sensing
WO2008066921A2 (en) * 2006-11-30 2008-06-05 Sensors For Medicine And Science, Inc. Oxidation resistant indicator molecules
JP2010517693A (en) * 2007-02-06 2010-05-27 グルメトリクス， インコーポレイテッド Optical system and method for ratiometric measurement of blood glucose concentration
US7824918B2 (en) 2007-08-06 2010-11-02 Glumetrics, Inc. HPTS-Mono and BIS Cys-Ma polymerizable fluorescent dyes for use in analyte sensors
US7751863B2 (en) 2007-02-06 2010-07-06 Glumetrics, Inc. Optical determination of ph and glucose
US8088097B2 (en) 2007-11-21 2012-01-03 Glumetrics, Inc. Use of an equilibrium intravascular sensor to achieve tight glycemic control
US8732188B2 (en) 2007-02-18 2014-05-20 Abbott Diabetes Care Inc. Method and system for providing contextual based medication dosage determination
US8930203B2 (en) 2007-02-18 2015-01-06 Abbott Diabetes Care Inc. Multi-function analyte test device and methods therefor
US8123686B2 (en) 2007-03-01 2012-02-28 Abbott Diabetes Care Inc. Method and apparatus for providing rolling data in communication systems
US7928850B2 (en) 2007-05-08 2011-04-19 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US8456301B2 (en) 2007-05-08 2013-06-04 Abbott Diabetes Care Inc. Analyte monitoring system and methods
US8665091B2 (en) 2007-05-08 2014-03-04 Abbott Diabetes Care Inc. Method and device for determining elapsed sensor life
US8461985B2 (en) 2007-05-08 2013-06-11 Abbott Diabetes Care Inc. Analyte monitoring system and methods
WO2008141241A1 (en) * 2007-05-10 2008-11-20 Glumetrics, Inc. Equilibrium non-consuming fluorescence sensor for real time intravascular glucose measurement
WO2008141243A2 (en) * 2007-05-10 2008-11-20 Glumetrics, Inc. Device and methods for calibrating analyte sensors
WO2008153930A1 (en) * 2007-06-08 2008-12-18 The Charles Stark Draper Laboratory, Inc. Sensors for the detection of diols and carbohydrates using boronic acid chelators for glucose
US20090014340A1 (en) * 2007-06-15 2009-01-15 Williams John R Devices, systems, and methods for measuring glucose
JP5675350B2 (en) 2007-07-11 2015-02-25 メドトロニック ミニメド インコーポレイテッド Polyviologen compound, method for synthesizing the compound, glucose sensor, and composition for measuring glucose
US20090247984A1 (en) * 2007-10-24 2009-10-01 Masimo Laboratories, Inc. Use of microneedles for small molecule metabolite reporter delivery
WO2009129186A2 (en) 2008-04-17 2009-10-22 Glumetrics, Inc. Sensor for percutaneous intravascular deployment without an indwelling cannula
US8181531B2 (en) * 2008-06-27 2012-05-22 Edwin Carlen Accessible stress-based electrostatic monitoring of chemical reactions and binding
US9011670B2 (en) * 2008-08-14 2015-04-21 The Charles Stark Draper Laboratory, Inc. Three-dimensional metal ion sensor arrays on printed circuit boards
US8103456B2 (en) 2009-01-29 2012-01-24 Abbott Diabetes Care Inc. Method and device for early signal attenuation detection using blood glucose measurements
US9226701B2 (en) 2009-04-28 2016-01-05 Abbott Diabetes Care Inc. Error detection in critical repeating data in a wireless sensor system
US9184490B2 (en) 2009-05-29 2015-11-10 Abbott Diabetes Care Inc. Medical device antenna systems having external antenna configurations
US9314195B2 (en) 2009-08-31 2016-04-19 Abbott Diabetes Care Inc. Analyte signal processing device and methods
WO2011026148A1 (en) 2009-08-31 2011-03-03 Abbott Diabetes Care Inc. Analyte monitoring system and methods for managing power and noise
WO2011041469A1 (en) 2009-09-29 2011-04-07 Abbott Diabetes Care Inc. Method and apparatus for providing notification function in analyte monitoring systems
JP2013506503A (en) 2009-09-30 2013-02-28 グルメトリクス， インコーポレイテッド Sensor with antithrombogenic coating
US8467843B2 (en) 2009-11-04 2013-06-18 Glumetrics, Inc. Optical sensor configuration for ratiometric correction of blood glucose measurement
WO2011097586A1 (en) 2010-02-08 2011-08-11 Glumetrics, Inc. Antioxidant protection of a chemical sensor
WO2011113020A1 (en) * 2010-03-11 2011-09-15 Glumetrics, Inc. Measurement devices and methods for measuring analyte concentration incorporating temperature and ph correction
US8822722B2 (en) * 2010-09-30 2014-09-02 Terumo Kabushiki Kaisha Fluorescent hydrogel and method for producing the same, and sensor for measuring saccharides using the same
US9681824B2 (en) 2011-03-15 2017-06-20 Senseonics, Incorporated Integrated catalytic protection of oxidation sensitive materials
EP2769226B1 (en) 2011-07-15 2017-05-24 Medtronic Minimed, Inc. Combinations of fluorphores and pyridinium boronic acid quenchers for use in analyte sensors
US9980669B2 (en) 2011-11-07 2018-05-29 Abbott Diabetes Care Inc. Analyte monitoring device and methods
JP5964960B2 (en) 2012-06-26 2016-08-03 京セラ株式会社 Sensor, detection method, and detection system
US9968306B2 (en) 2012-09-17 2018-05-15 Abbott Diabetes Care Inc. Methods and apparatuses for providing adverse condition notification with enhanced wireless communication range in analyte monitoring systems
KR101517963B1 (en) 2012-11-09 2015-05-06 한국세라믹기술원 Water sensitive phosphor, manufacturing method thereof and water and defection detecting sensor comprising said water sensitive phosphor
US9181389B2 (en) * 2013-05-20 2015-11-10 Xerox Corporation Alizarin-based polymer colorants
KR101440547B1 (en) 2013-05-20 2014-09-17 한국화학연구원 Anthracene derivatives for metal ions, preparation method thereof and selective detection method of metal ions using the same
US9963556B2 (en) 2013-09-18 2018-05-08 Senseonics, Incorporated Critical point drying of hydrogels in analyte sensors
WO2016014987A2 (en) 2014-07-24 2016-01-28 Thomas Jefferson University Long-term implantable monitoring system & methods of use
US10716500B2 (en) 2015-06-29 2020-07-21 Cardiac Pacemakers, Inc. Systems and methods for normalization of chemical sensor data based on fluid state changes
CN115505280A (en) 2016-12-21 2022-12-23 普罗菲尤萨股份有限公司 Polymerizable near infrared dyes
JOP20190161A1 (en) 2016-12-27 2017-06-16 Profusa Inc Near-ir glucose sensors
WO2018184012A1 (en) 2017-03-31 2018-10-04 Capillary Biomedical, Inc. Helical insertion infusion device
CN108968976B (en) 2017-05-31 2022-09-13 心脏起搏器股份公司 Implantable medical device with chemical sensor
CN109381195B (en) 2017-08-10 2023-01-10 心脏起搏器股份公司 Systems and methods including electrolyte sensor fusion
CN109419515B (en) 2017-08-23 2023-03-24 心脏起搏器股份公司 Implantable chemical sensor with staged activation
CN109864746B (en) 2017-12-01 2023-09-29 心脏起搏器股份公司 Multimode analyte sensor for medical devices
CN109864747B (en) 2017-12-05 2023-08-25 心脏起搏器股份公司 Multimode analyte sensor optoelectronic interface
CA3104346A1 (en) * 2018-06-27 2020-01-02 Profusa, Inc. Near-ir glucose sensors

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2284809B (en) * 1993-11-07 1998-04-29 Japan Res Dev Corp A fluorescent phenylboronic acid suitable for use in the detection of saccharides
US5516645A (en) * 1994-04-25 1996-05-14 Johnson & Johnson Clinical Diagnostics, Inc. Immunoassay analytical elements containing vanadium IV(V+4)ions
US5998594A (en) * 1994-12-30 1999-12-07 University Of Pittsburgh Of The Commonwealth System Of Higher Education Self-assembling, chromogenic receptors for the recognition of medically important substrates and their method of use
JP2799837B2 (en) 1995-03-03 1998-09-21 科学技術振興事業団 Boronic acid compounds having a binaphthyl group
US6063637A (en) * 1995-12-13 2000-05-16 California Institute Of Technology Sensors for sugars and other metal binding analytes
CA2322858C (en) * 1998-03-11 2009-06-02 Sensors For Medicine And Science, Inc. Detection of analytes by fluorescent lanthanide chelates
US6511814B1 (en) * 1999-03-26 2003-01-28 Idexx Laboratories, Inc. Method and device for detecting analytes in fluids
US6366793B1 (en) * 1999-09-10 2002-04-02 Beckman Coulter, Inc. Minimally invasive methods for measuring analtes in vivo
WO2002012251A1 (en) * 2000-08-04 2002-02-14 Sensors For Medicine And Science, Inc. Detection of analytes in aqueous environments
US20020127626A1 (en) * 2001-01-05 2002-09-12 Sensors For Medicine And Science, Inc. Detection of glucose in solutions also containing an alpha-hydroxy acid or a beta-diketone

Also Published As

Publication number Publication date
US7078554B2 (en) 2006-07-18
KR101012325B1 (en) 2011-02-08
EP1490359B1 (en) 2010-05-19
JP4431398B2 (en) 2010-03-10
AU2003220293A1 (en) 2003-09-29
BR0308412A (en) 2005-03-29
EP1490359A4 (en) 2006-08-23
EP1490359A1 (en) 2004-12-29
JP2005530130A (en) 2005-10-06
US20050043275A1 (en) 2005-02-24
US20030082663A1 (en) 2003-05-01
CA2478979C (en) 2011-09-20
MXPA04008931A (en) 2004-12-13
AU2003220293B2 (en) 2009-10-15
KR20040091138A (en) 2004-10-27
WO2003078424A1 (en) 2003-09-25
US6800451B2 (en) 2004-10-05

Similar Documents

Publication Publication Date Title
CA2478979A1 (en) Detection of glucose in solutions also containing an alpha-hydroxy acid or a beta-diketone
Maruyama et al. A novel, cell-permeable, fluorescent probe for ratiometric imaging of zinc ion
Rae et al. Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase
Lo et al. Non-covalent binding of luminescent transition metal polypyridine complexes to avidin, indole-binding proteins and estrogen receptors
CA2222556C (en) Adduct protection assay
US6919463B2 (en) Signalling compounds for use in methods of detecting hydrogen peroxide
US20020127626A1 (en) Detection of glucose in solutions also containing an alpha-hydroxy acid or a beta-diketone
US20090253161A1 (en) Fluorescent prochelators for cellular iron detection
Hao et al. Mapping of heavy metal ion sorption to cell-extracellular polymeric substance-mineral aggregates by using metal-selective fluorescent probes and confocal laser scanning microscopy
AU623038B2 (en) Improved composition, device and method of assaying for peroxidatively active substances
JPH02503268A (en) protected chemiluminescent label
CA2433904A1 (en) Detection of analytes
CA2300096A1 (en) Methods and compositions for generating chemiluminescence with peroxidase enzymes
Tse Sum Bui et al. Escherichia coli biotin synthase produces selenobiotin. Further evidence of the involvement of the [2Fe-2S] 2+ cluster in the sulfur insertion step
Wang et al. A spectrofluorimetric method for cysteine and glutathione using the fluorescence system of Zn (II)–8-hydroxyquinoline-5-sulphonic acid complex
Shepherd et al. Fluorescence energy transfer measurements in the pyruvate dehydrogenase multienzyme complex from Escherichia coli with chemically modified lipoic acid
US20020090734A1 (en) Detection of glucose in solutions also containing an alpha-hydroxy acid or a beta-diketone
CA2491692A1 (en) Reagents and a method for saturation labelling of proteins
Walsh et al. The pH dependence of the emitting properties of ruthenium polypyridyl complexes bound to poly-l-lysine
Thomas SYNTHESIS AND EVALUATION OF FLUORESCENT REAGENTS FOR THE STUDY OF NUCLEIC ACIDS AND PROTEINS.
Jacobson DISTANCE RELATIONSHIPS BETWEEN THE CATALYTIC, GTP AND ADP REGULATORY SITES OF GLUTAMATE DEHYDROGENASE LABELED WITH FLUORESCENT NUCLEOTIDE ANALOGUES (5'-P-FLUOROSULFONYLBENZOYL-1, N (6)-ETHENOADENOSINE)

Legal Events

Date Code Title Description
EEER Examination request
MKLA Lapsed

Effective date: 20150316

MKLA Lapsed

Effective date: 20150316