SMMR (small molecule metabolite reporters) for use as in vivo glucose biosensors
View Patent ↗Small Molecule Metabolite Reporters (SMMRs) for use as in vivo glucose biosensors, sensor compositions, and methods of use, are described. The SMMRs include boronic acid-containing xanthene, coumarin, carbostyril and phenalene-based small molecules which are used for monitoring glucose in vivo, advantageously on the skin.
1. A small molecule metabolite reporter compound having a structure represented by the following formula:
wherein:
D is O or N;
R 9 is H, CH 3 , M,
or taken together with R 10 and the ring to which they are attached, forms a substituted benzene ring;
R 10 is H, CH 3 , M, B(OH) 2 , or
or taken together with R 9 and the ring to which they are attached, forms the substituted benzene ring;
M is
wherein L is an amino-containing linking moiety; and
at least one boronic acid moiety is present in the compound; and salts thereof.
2. The compound of claim 1 , wherein D is O.
3. The compound of claim 1 , wherein D is N.
4. The compound of claim 1 , wherein at least one of R 9 and R 10 , is M, and wherein M has a structure represented by Formula (A):
5. The compound of claim 4 , wherein R 10 is M, and wherein M has a structure represented by Formula (A).
6. The compound of claim 1 , wherein at least one of R 9 and R 10 , is M, and wherein M has a structure represented by Formula (B):
7. The compound of claim 6 , wherein R 9 is M, and wherein M has a structure represented by Formula (B).
8. The compound of claim 1 , wherein at least one of R 9 and R 10 , is M, and wherein M has a structure represented by Formula (C):
9. A method of measuring a compound or metabolite thereof, comprising:
containing the compound of claim 1 with an area of a mammalian body where the compound or metabolite may be found; and
detecting a photometric change in the compound, wherein the change is indicative of a property of the compound or metabolite thereof.
10. The method of claim 9 , wherein the compound is glucose.
11. The method of claim 9 , wherein the area of the body is skin.
12. The method of claim 9 , wherein the area of the body is the stratum corneum.
13. The method of claim 9 , wherein the area of the body is the epidermis.