Multi-sensor array compound and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10017525-B2
Application number	US-201314414916-A
Country	US
Kind code	B2
Filing date	Jul 16, 2013
Priority date	Jul 16, 2012
Publication date	Jul 10, 2018
Grant date	Jul 10, 2018

Abstract

The present invention is directed to a multi-sensor array compound including at least three chromophores, at least one receptor and an anchor. Contacting the compound of this invention with an analyte (such as carbohydrate) forms a complex with unique optical signature. The unique optical signature allows differentiating between carbohydrates, diagnosing diseases associated with the carbohydrate, and encoding information in an encoding system.

First claim

The invention claimed is:

1. A compound comprising an array of at least three chromophores, at least one receptor and an anchor, wherein binding said receptor to an analyte results in a unique optical signature; wherein said receptor is a boronic acid receptor, wherein said anchor is cis-amino L proline, trans-amino-L proline, cis-amino-D L proline or trans-amino-D proline and wherein said chromophore is attached to said anchor via a linker, wherein said linker comprises nitrogen.

2. The compound of claim 1 , wherein said at least three chromophores are the same or different.

3. The compound of claim 1 , wherein said chromophore is naphthalene, anthracene, fluorenyl, dansyl or any combination thereof.

4. The compound of claim 1 , wherein said receptor is phenyl boronic acid.

5. The compound of claim 1 , wherein said analyte is antibiotic selected from: macrolides, aminoglycosides, cardiac glycosides or rifamycins; or carbohydrate selected from: L-Glucose, D-Glucose, D-fructose, L-fructose, D-arabinose, D-xylose, L-xylose, L-mannose, D-galactose, D-sorbitol, mannitol, dulcitol, adonitol, xylitol, L-threitol, maltitol, lactulose, D-lactose, D-maltose, D-trehalose or maltotriose.

6. The compound of claim 1 , wherein said compound is represented by the following structure 1:

7. The compound of claim 1 , wherein a first fluorescent dye emits at a wavelength which is the absorption wavelength of a second fluorescent dye.

8. The compound of claim 1 , wherein a first fluorescent dye is naphthalene, fluorenyl or combination thereof, wherein said first fluorescent dye emits light at a wavelength of between 300-370 nm following excitation at 270 nm; wherein said second fluorescent dye is dansyl, anthracene or combination thereof, wherein said second fluorescent dye absorbs at a range of between 300 to 400 nm.

9. A method of differentiating between carbohydrates comprising:
contacting a carbohydrate with a compound in a liquid medium, wherein said carbohydrate and said compound form a complex; wherein said compound comprises an array of at least three chromophores, at least one boronic acid receptor and an anchor; wherein said anchor is cis-amino-L proline, trans-amino-L proline, cis-amino-D proline or trans-amino-D proline and wherein said chromophore is attached to said anchor via a linker, wherein said linker comprises nitrogen; wherein contacting said carbohydrate with said compound results in a conformational change of said compound and thereby to a unique optical signature of said complex; and
measuring the optical signature of said complex;
and thereby, differentiating said carbohydrate.

10. The method of claim 9 , wherein said chromophore is naphthalene, anthracene, fluorenyl, dansyl or any combination thereof.

11. The method of claim 9 , wherein said carbohydrate is antibiotic or a saccharide, wherein said saccharide is L-Glucose, D-Glucose, D-fructose, L-fructose, D-arabinose, D-xylose, L-xylose, L-mannose, D-galactose, D-sorbitol, mannitol, dulcitol, adonitol, xylitol, L-threitol, maltitol, lactulose, D-lactose, D-maltose, D-trehalose or maltotriose; wherein said antibiotic is macrolides, aminoglycosides, cardiac glycosides, or rifamycins.

12. The method of claim 9 , wherein said receptor is phenyl boronic acid.

13. The method of claim 9 , wherein said compound is represented by the following structure 1:

14. The method of claim 9 , wherein said unique optical signature is a fluorescence pattern of said complex; and said fluorescence pattern is obtained followed irradiation of said complex at a wavelength that at least one of said fluorescent dye is excited.

15. The method of claim 14 , wherein said fluorescence pattern indicates the presence of at least one carbohydrate in said medium.

16. The method of claim 9 , wherein said liquid medium is an aqueous solution.

17. The method of claim 9 , wherein said carbohydrate is a component of a glycoprotein, a proteoglycan or a glycolipid.

18. The method of claim 11 , wherein said saccharide is a monosaccharide, a disaccharide or a glycan independent of a protein or lipid compound.

19. A method of diagnosing a disease in a subject, wherein said diagnosis comprises detection of a carbohydrate biomarker; said method comprising:
collecting a biological sample from a subject;
optionally isolating components from said biological sample;
contacting a compound with a carbohydrate comprised within said sample or isolated component in a liquid medium; wherein said carbohydrate forms a complex with said compound; wherein said compound comprises an array of at least three chromophores, at least one boronic acid receptor and an anchor; wherein said anchor is cis-amino-L proline, trans-amino-L proline, cis-amino-D proline or trans-amino-D proline and wherein said chromophore is attached to said anchor via a linker, wherein said linker comprises nitrogen; wherein contacting said compound with said carbohydrate results in a conformational change of said compound and thereby to a unique optical signature of said complex;
measuring the optical signature of said complex;
identifying a carbohydrate biomarker in said sample, said carbohydrate biomarker being characteristic of a disease; or measuring a change in a concentration of a carbohydrate biomarker in said sample compared to normative values, wherein said change is characteristic of a disease;

thereby, diagnosing a disease in a subject.

20. The method of claim 19 wherein said chromophore is naphthalene, anthracene, fluorenyl, dansyl or any combination thereof.

21. The method of claim 19 wherein said carbohydrate is L-Glucose, D-Glucose, D-fructose, L-fructose, D-arabinose, D-xylose, L-xylose, L-mannose, D-galactose, D-sorbitol, mannitol, dulcitol, adonitol, xylitol, L-threitol, maltitol, lactulose, D-lactose, D-maltose, D-trehalose or maltotriose.

22. The method of claim 19 wherein said receptor is phenyl boronic acid.

23. The method of claim 19 wherein said compound is represented by the following structure 1:

24. The method of claim 19 wherein said unique optical signature is a fluorescence pattern of said complex; and said fluorescence pattern is obtained followed irradiation of said complex at a wavelength that at least one of said fluorescent dye is excited.

25. The method of claim 19 wherein said disease is selected from hypoglycemia, prostate cancer, diabetes, syndrome X or a glycoprotein based disease selected from multiple sclerosis, crohn's disease, autoimmune disease, colitis, inflammatory bowel disease, cancer, lysosomal storage disease, or celiac.

26. The method of claim 19 , wherein said carbohydrate biomarker is a component of a glycoprotein, a glycolipid or a proteoglycan.

27. The method of claim 19 , wherein said carbohydrate biomarker is a monosaccharide, a disaccharide or a glycan independent of a protein or lipid molecule.

Assignees

• Yeda Res & Dev
• Yeda Res & Dev

Inventors

• Margulies David
• Rout Bhimsen

Classifications

• G01N33/582

  with fluorescent label · CPC title

• C09B62/44

  with the reactive group not directly attached to a heterocyclic ring · CPC title

• G01N2800/042

  Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism · CPC title

• G01N2400/00

  Assays, e.g. immunoassays or enzyme assays, involving carbohydrates · CPC title

• G01N2458/30

  Electrochemically active labels · CPC title