Fluorescent sensor compounds for detecting saccharides

• US 20040048390A1
• Filed: 05/13/2003
• Published: 03/11/2004
• Est. Priority Date: 05/14/2002
• Status: Active Grant

• Current Assignee: North Carolina State University (University of North Carolina System)
• Original Assignee: North Carolina State University (University of North Carolina System), University of South Carolina
• Inventors: Wang, Binghe, Yang, Wenqian, Weston, Brent
• Granted Patent: US 6,916,660 B2
• Time in Patent Office: Days
• US Class Current: 436/172
• CPC Class Codes: A61K 31/69 Boron compounds
• CPC Class Codes: C07F 5/025 Boronic and borinic acid compounds
• CPC Class Codes: G01N 33/57492 involving compounds localized on the membrane of tumor or cancer cells
• CPC Class Codes: G01N 33/66 involving blood sugars, e.g. galactose
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

Fluorescent sensor compounds having the formula:

wherein L is selected from the group consisting of alkyl, alkylene, aryl, cycloalkyl, alkoxy, aryloxy, arylalkyl, and arylalkyloxyl;

each m, m′, n, n′, p, and p′ is independently an integer from 0 to 4, inclusive; and

each R₁, R′₁, R₂, R′₂, R₃ and R′₃ is independently selected from the group consisting of hydrogen, alkyl, alkylene, aryl, cycloalkyl, alkoxy, aryloxy, arylalkyl, arylalkyloxyl, halo, substituted and unsubstituted amino, and substituted and unsubstituted thiol, are useful for the selective detection of saccharides such as glucose and sialyl Lewis X. The compounds find particular use in detecting saccharides in biological samples, and in detecting cancer cells that express cell surface polysaccharides such as sialyl Lewis X.

Claims

1. A fluorescent sensor compound having the formula:

2. The compound according to claim 1, wherein L is selected from the group consisting of C₂ to C₂₀ alkyl.

3. The compound according to claim 1, wherein L is aryl.

4. The compound according to claim 1, wherein L is selected from the group consisting of:

5. The compound according to claim 1, wherein L is selected from the group consisting of:

6. The compound according to claim 1, wherein m, m′

, n, n′

, p, and p′

are each zero and L is;

7. The compound according to claim 1, wherein m, m′

, n, n′

, p, and p′

are each zero and L is;

8. The compound according to claim 1, wherein the compound selectively binds a saccharide.

9. The compound according to claim 8, wherein the saccharide is a monosaccharide.

10. The compound according to claim 9, wherein the monosaccharide is glucose.

11. The compound according to claim 8, wherein the saccharide is a polysaccharide.

12. The compound according to claim 11, wherein the polysaccharide is a cell-surface polysaccharide.

13. The compound according to claim 11, wherein the polysaccharide is sialyl Lewis X (sLex).

14. A method of detecting glucose in a biological sample, comprising contacting a biological sample with a fluorescent sensor compound having the formula:

15. The method according to claim 14, further comprising

measuring the amount of fluorescence in the sample;

and

correlating the amount of fluorescence in the sample with a concentration of glucose in the sample.

16. The method according to claim 14, wherein m, m′

, n, n′

, p, and p′

are each zero and L is;

17. The method according to claim 14, wherein the fluorescent sensor compound is provided in an implantable sensor device.

18. A method of detecting sialyl Lewis X in a biological sample, comprising contacting a biological sample with a fluorescent sensor compound having a formula:

19. The method according to claim 18, further comprising:

measuring the amount of fluorescence in the sample; and

correlating the amount of fluorescence in the sample with a concentration of sialyl Lewis X in the sample.

20. The method according to claim 18, wherein m, m′

, n, n′

, p, and p′

are each zero and L is;

21. A method of detecting cancer cells that express sialyl Lewis X in a biological sample, comprising contacting a biological sample with a fluorescent sensor compound of the formula:

22. The method according to claim 21, further comprising:

measuring the amount of fluorescence in the sample; and

correlating the amount of fluorescence in the sample with the amount of cancerous cells in the sample.

23. The method according to claim 21, wherein m, m′

, n, n′

, p, and p′

are each zero and L is;

24. The method according to claim 21, wherein the cancer cells are carcinoma cells.

25. The method according to claim 21, wherein the cancer cells are hepatocellular carcinoma cells.