Glucose sensor molecules

1. A glucose sensor comprising a glucose receptor having a binding site of formula (I):

wherein X represents O or S;

n is from 1 to 4;

m is from 1 to 4, and n+m is 5;

each R 1 is the same or different and represents hydrogen, C 1-4 alkyl or C 3-7 cycloalkyl;

or R 1 , together with an adjacent R 1 group and the carbon or nitrogen atoms to which they are attached, form a C 3-7 cycloalkyl or a 5- or 6-membered heterocyclyl group.

2. A glucose sensor according to claim 1 , wherein X represents O.

3. A glucose sensor according to claim 1 , wherein each R 1 is the same or different and represents hydrogen, C 1-4 alkyl or C 3-7 cycloalkyl; and R 2 represents hydrogen or C 1-4 alkyl.

4. A glucose sensor according to claim 1 , wherein at least four R 1 groups represent hydrogen.

5. A glucose sensor according to claim 1 , wherein

X represents O;

n is from 1 to 4;

m is from 1 to 4 and n+m is 5; and

each R 1 represents hydrogen.

6. A glucose sensor according to claim 5 , wherein n is 2 or 3, m is 2 or 3 and n+m is 5.

7. A glucose sensor according to claim 1 , wherein the glucose receptor is bonded to a support material at one of the nitrogen atoms marked as N*:

8. A glucose sensor according to claim 7 , wherein the support material is a dendrimer or water-soluble polymer and the resulting complex of receptor and support material is in aqueous solution.

9. A glucose sensor according to claim 1 , wherein the sensor further comprises a fluorophore, the fluorophore being associated with the glucose receptor such that when glucose is bound to the receptor, the fluorescence of the fluorophore is perturbed.

10. A glucose sensor according to claim 1 , wherein the sensor comprises a glucose sensor molecule of formula (II):

wherein X, n, m and R 1 are as defined in claim 1 ;

Fl is a fluorophore;

L 1 and L 2 are the same or different and represent a linker; and

R 4 is a support material or a hydrogen atom.

11. A glucose sensor according to claim 10 , wherein L 1 and L 2 are the same or different and each consists of one or more C 1-6 alkylene groups and/or one or more arylene groups.

12. A glucose sensor according to claim 11 , wherein L 2 is a group of formula —(CH 2 ) s -Ph-(CH 2 ) t —, wherein s is 1 or 2, t is 0, 1 or 2 and Ph is phenylene; and/or L 1 is methylene or ethylene.

13. A glucose sensor according to claim 10 , wherein the sensor comprises a glucose sensor molecule of formula (II′) or (II″):

wherein

Fl is a fluorophore; and

R 4 is a support material or a hydrogen atom.

14. A glucose sensor according to claim 10 , wherein R 4 is a support material and the support material is a polymeric matrix, a water-soluble polymer or a water soluble molecule selected from dendrimers, cyclodextrins, cryptans and crown ethers.

15. A glucose sensor molecule of formula (II):

wherein X, n, m and R 1 are as defined in claim 1 ;

Fl is a fluorophore;

L 1 and L 2 are the same or different and represent a linker; and

R 4 is a support material, a hydrogen atom or an anchor group suitable for attaching the sensor molecule to a support material, wherein the support material is selected from the group consisting of a polymeric matrix, a water-soluble polymer or a water soluble molecule selected from dendrimers, cyclodextrins, cryptans, and crown ethers.

16. A glucose sensor molecule according to claim 15 , wherein R 4 is an anchor group selected from an alkene, ester, aldehyde, amine or azide group.

17. A process for the preparation of a glucose sensor molecule as claimed in claim 15 , which process comprises reductive amination of (III) in the presence of (IV), followed by deprotection of the boronic acid group:

Fl-L 1 -NH—(CHR 1 ) n —X—(CHR 1 ) m —NH-L 2 -R 4   (III)

wherein X, n, m and R 1 are as defined in claim 1 ;

Fl is a fluorophore;

L 1 and L 2 are the same or different and represent a linker; and

R 4 is a hydrogen atom or an anchor group suitable for attaching the sensor molecule to a support material;

wherein B(PG) is a boronic acid group protected by a protecting group.

18. A method of detecting or quantifying the amount of glucose in an analyte, the method comprising contacting the analyte with a glucose receptor comprising a binding site of formula (I):

wherein X, n, m and R 1 are as defined in claim 1 .

19. A method according to claim 18 , which method is a fluorescence sensing method comprising detecting a change in the fluorescence of the sensor when glucose is bound to the glucose receptor.

20. A method according to claim 19 , wherein the change in fluorescence is a change in fluorescence lifetime.

21. A process according to claim 17 , wherein the change in fluorescence is a change in fluorescence intensity.

22. A process for the preparation of a glucose sensor molecule as claimed in claim 15 , which process comprises reductive amination of (III) in the presence of (IV), followed by deprotection of the boronic acid group and deprotection of R 4 :

Fl-L 1 -NH—(CHR 1 ) n —X—(CHR 1 ) m —NH-L 2 -R 4   (III)

wherein X, n, m and R 1 are as defined in claim 1 ;

Fl is a fluorophore;

L 1 and L 2 are the same or different and represent a linker; and

R 4 is a hydrogen atom or an anchor group suitable for attaching the sensor molecule to a support material, wherein R 4 is protected by a protecting group;

wherein B(PG) is a boronic acid group protected by a protecting group.

23. A glucose sensor molecule according to claim 15 wherein L 1 and L 2 are the same or different and each consists of one or more C 1-6 alkylene groups and/or one or more arylene groups.

24. A glucose sensor molecule according to claim 15 , wherein L 2 is a group of formula —(CH 2 ) s -Ph-(CH 2 ) t —, wherein s is 1 or 2, t is 0, 1 or 2 and Ph is phenylene; and/or L 1 is methylene or ethylene.