Probes for detection of copper

Patent metadata

Field	Value
Publication number	US-12241902-B2
Application number	US-202017603205-A
Country	US
Kind code	B2
Filing date	Apr 29, 2020
Priority date	May 8, 2019
Publication date	Mar 4, 2025
Grant date	Mar 4, 2025

Abstract

The present disclosure provides Forster resonance energy transfer (FRET)-based probes for detecting copper, e.g., for detecting Cu(I) in live cells. The present disclosure provides methods for detecting copper, e.g., for detecting Cu(I) in live cells, using a FRET-based probe of the present disclosure.

First claim

What is claimed is:

1. A compound of the formula (I):
A-X1-E-X2-D   (I)

wherein:
A is a Förster resonance energy transfer (FRET) acceptor group,
D is a FRET donor group,
E is a Cu(I)-coordinating group,
X1 and X2 are linking groups.

2. The compound of claim 1 , wherein X1, X2, or both X1 and X2 are cleavable by Cu(I).

3. The compound of claim 2 , wherein X1 and not X2 is cleavable by Cu(I) or wherein X2 and not X1 is cleavable by Cu(I).

4. The compound of claim 2 , wherein at least one of the A-X1 moiety and the X2-D moiety comprises a C—O bond cleavable by Cu(I).

5. The compound of claim 4 , wherein the compound comprises the structure of formula (II):

wherein a C—O group of formula (II) is cleavable by Cu(I),
wherein R 4 , R 5 , and R 6 are each independently selected from H or a hydrocarbon group.

6. The compound of claim 5 , wherein the compound comprises the structure of formula (III):

7. The compound of claim 2 , wherein at least one of the A-X1 moiety and the X2-D moiety comprises a C—N bond cleavable by Cu(I).

8. The compound of claim 1 , wherein E has a formula selected from:

wherein each Z is a coordination group,
wherein L z is a linker,
wherein E is a tridentate or tetradentate group.

9. The compound of claim 8 , wherein each Z is independently selected from:

a functionalized thioether, and derivatives and homologs thereof,
wherein m is 0 or 1,
wherein n is 0 or 1,
wherein p is 1 or 2,
wherein q is 1 or 2,
wherein r is 1 or 2,
wherein each of R 1 , R 2 , and R 3 are independently selected from H and an alkyl group.

10. The compound of claim 8 , wherein E has the formula (VIII).

11. The compound of claim 10 , wherein Z 1 is NR 1 R 2 R 3 and wherein each of R 1 , R 2 , and R 3 is an alkyl group.

12. The compound of claim 11 , wherein Z 2 , Z 3 , and Z 4 are each comprise a pyridine group.

13. The compound of claim 12 , wherein E comprises the structure (XII):

wherein s1, s2, and s3 are each independently selected from 0, 1, 2, 3, 4, and 5.

14. The compound of claim 13 , wherein E comprises the structure (XIII):

15. The compound of claim 14 , wherein the composition comprises the structure (XIV):

16. The composition of claim 8 , wherein:
a) E has the formula (VIII) or (IX) and each Z comprises a pyridine group;
b) wherein E has the formula (V), (VI) or (VII) and Z 1 is a bidentate group;
c) wherein E has the formula (V) and wherein Z 1 and Z 2 are each a bidentate group;
d) wherein E has the formula (VI) or (VII) or (VIII), or (IX), and wherein at least one Z comprises NR 1 R 2 R 3 ; or
e) wherein E has the formula (IV) or (V), and wherein Z 1 has the formula (X), (XI), 15-crown-5, 18-crown-6, or a functionalized thioether.

17. The compound of claim 1 , wherein A comprises a small molecule dye group, a fluorescent protein group, or a quantum dot.

18. The compound of claim 1 , wherein A has an excitation maximum between 500 nm and 600 nm, and wherein D has an excitation maximum between 450 nm and 525 nm.

19. The compound of claim 1 , wherein D comprises a small molecule dye group, a fluorescein group, a fluorescent protein group, or a quantum dot.

20. A method of detecting Cu(I) in a living cell, the method comprising:
a) contacting the cell with a compound according to claim 1 ; and
b) detecting ratiometric emission from the probe.

Assignees

• Univ California

Inventors

• Chang Christopher J
• Chung Yik Sham Clive
• Lee Sumin

Classifications

• C07D405/14

  containing three or more hetero rings · CPC title

• A61K49/0041

  Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal (in vivo G01N) · CPC title

• G01N33/84 Primary

  involving inorganic compounds or pH · CPC title

• A61K49/0043 Primary

  Fluorescein, used in vivo · CPC title