Rotaxane-type probe for molecular imaging

Patent metadata

Field	Value
Publication number	US-11045561-B2
Application number	US-201815939261-A
Country	US
Kind code	B2
Filing date	Mar 28, 2018
Priority date	Mar 28, 2017
Publication date	Jun 29, 2021
Grant date	Jun 29, 2021

Abstract

The invention provides a novel method for synthesizing hyperpolarized xenon-129 (HP Xe) biosensors by using pseudo-rotaxane structures of gamma-cyclodextrin. These supramolecular complexes form novel ternary structures in the presence of HP Xe which can be detected via 129 Xe MR spectroscopy and imaging techniques. The rotaxane-type complex can be tagged with an affinity label for detecting a target in a biological subject.

First claim

What is claimed is:

1. A supramolecular complex useful as a biosensor, comprising:
(a) a macrocycle host defining a hydrophobic cavity;
(b) an axle comprising a molecular chain functionalized with an affinity tag for a target inside a biological subject, wherein the affinity tag is at one or both ends of the molecular chain, and wherein the axle is threaded through the macrocycle cavity; and
(c) a xenon atom, wherein the cavity of the macrocycle host is large enough to accommodate and reversibly encapsulate both a cross section of the axle and the xenon atom at the same time.

2. The supramolecular complex of claim 1 , wherein the macrocycle host is water-soluble.

3. The supramolecular complex of claim 1 , wherein the xenon atom is dissolved in a solution.

4. The supramolecular complex of claim 1 , wherein the macrocycle host defines a cavity that is larger than about 6.5 Å in inner diameter.

5. The supramolecular complex of claim 1 , wherein the macrocycle host is a cyclodextrin.

6. The supramolecular complex of claim 5 , wherein the macrocycle host is a γ-cyclodextrin.

7. The supramolecular complex of claim 1 , wherein the axle comprises an alkyl chain.

8. The supramolecular complex of claim 7 , wherein the axle has at least five carbons in its backbone.

9. The supramolecular complex of claim 1 , wherein the axle is capped with a hydrophobic end group at each of its two ends, at least one of the end groups being or comprising the affinity tag.

10. The supramolecular complex of claim 1 , wherein the affinity tag comprises a ligand selected for its affinity for a biological target inside a subject.

11. The supramolecular complex of claim 1 , wherein the affinity tag comprises a detectable label.

12. The supramolecular complex of claim 11 , wherein the affinity tag comprises a fluorophore.

13. The supramolecular complex of claim 1 , wherein the affinity tag comprises thioflavin T.

14. The supramolecular complex of claim 1 , detectable by xenon-based magnetic resonance imaging or spectroscopy.

15. A biosensor comprising:
(a) a cyclodextrin molecule defining a cavity;
(b) an alkyl chain molecule functionalized with an affinity tag at one or each of its two ends, wherein the affinity tag has an affinity for a target inside a biological subject, and wherein the alkyl chain molecule is threaded through the cavity in the cyclodextrin; and
(c) a xenon atom in the cavity of the cyclodextrin.

16. The biosensor of claim 15 , wherein the affinity tag comprises a detectable label.

17. The biosensor of claim 15 , wherein the affinity tag is part of an end group that also serves as a stopper to prevent de-threading.

18. The biosensor of claim 17 , wherein the end group is hydrophobic.

19. The biosensor of claim 17 , wherein the end group comprises an ethylimidazolium group or an anthracene group.

20. The biosensor of claim 15 , wherein the xenon atom is xenon-129.

Assignees

• Rhode Island Council On Postsecondary Education
• Univ Of Rhode Island Board Of Trustees

Inventors

• Deboef Brenton
• Fernando Ashvin

Classifications

• C08B37/0015 Primary

  Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes · CPC title

• C08L101/00

  Compositions of unspecified macromolecular compounds · CPC title

• C08G83/007

  Polyrotaxanes; Polycatenanes · CPC title

• G01N33/582

  with fluorescent label · CPC title

• G01N33/0021

  involving the use of a carrier gas for transport to the sensor · CPC title