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 of the following formula:
wherein
D is a heteroatom other than O;
R 1 and R 2 are different and are selected from the group consisting of H, OH, NO 2 , OCH 3 , A, or, R 1 and R 2 , taken together with the ring to which they are attached, form R 7 ;
R 3 and R 4 are different and are selected from the group consisting of H,
OH, B(OH) 2 , M, or R 3 and R 4 taken together with the ring to which they are attached, form R 8 ;
R 5 and R 6 are different and are selected from the group consisting of H or
wherein Q is H, COOH, or B(OH) 2 ;
A is OH, or
R 7 is
R 8 is
M is
L, when present, is an amino-containing linking moiety;
R 1 and R 2 , and R 3 and R 4 , are adjacent to each other on the rings on which they reside; and
at least one boronic acid moiety is present; and salts thereof.
2. The reporter compound of claim 1 , wherein D is N.
3. The small molecule metabolite reporter compound of claim 1 , wherein:
D is N;
R 1 and R 2 are different and are selected from the group consisting of H and OH;
R 3 and R 4 are different and are selected from the group consisting of H,
and OH; and
R 5 and R 6 are different and are selected from the group consisting of H or
wherein Q is H, COOH, or B(OH) 2 .
4. A small molecule metabolite reporter compound of the following formula:
wherein R 1 and R 2 together form R 7 ;
R 3 and R 4 are different and are selected from the group consisting of H, B(OH) 2 , or R 3 and R 4 taken together with the ring to which they are attached, form R 8 ;
R 6 is selected from the group consisting of H or
wherein Q is H, COOH, or B(OH) 2 ;
A is NH 3 ,
R 7 is
R 8 is;
at least one boronic acid moiety is present; and
R 1 and R 2 , and R 3 and R 4 , are adjacent to each other on the rings on which they reside; and salts thereof.
5. The small molecule metabolite reporter compound of claim 4 , wherein:
A is
R 3 and R 4 are different and are selected from the group consisting of H and B(OH) 2 ; and
R 6 is
wherein Q is H or COOH.
6. A topical sensor composition comprising a compound of any one of claims 1 , 2 , 4 , 5 , and 3 , and a carrier or binder.