Fluorescent dyes for use in glucose sensing
View Patent ↗A novel class of compounds that includes HPTS-Cys-MA, and methods of making them are disclosed herein. The class of compounds including HPTS-Cys-MA are useful as fluorescent dyes for analyte detection.
1. The compound:
wherein:
R 2 is
R 3 is —(CH 2 ) n —A − M + ,
wherein n is 1-4,
wherein A − is an anionic group selected from the group consisting of SO 3 − ,
HPO 3 − , CO 2 − and
and
wherein M + is a cationic group selected from the group consisting of H + , an alkali metal ion, Li + , Na + , K + , Rb + , Cs + , Fr + , an onium ion and NR 4 + , wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
R 4 is
R 5 is selected from the group consisting of
wherein n is equal to 1-10, n′ is equal to 2-4 and Y is selected from the group consisting of NH and O;
R 6 is selected from the group consisting of NHR 7 , OR 7 and CO 2 H; and
R 7 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl, acrylamido and methacrylamido.
2. The compound:
wherein:
R 3 is —(CH 2 ) n —A − M + ,
wherein n is 1-4,
wherein A − is an anionic group selected from the group consisting of SO 3 − ,
HPO 3 − , CO 2 − and
and
wherein M + is a cationic group selected from the group consisting of H + , an alkali metal ion, Li + , Na + , K + , Rb + , Cs + , Fr + , an onium ion and NR 4 + , wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
R 4 is
R 8 is selected from the group consisting of
wherein n is equal to 1-10, n′ is equal to 2-4;
R 9 is selected from the group consisting of NHR 10 , OR 10 and CO 2 H; and
R 10 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl, acrylamido and methacrylamido.
3. The compound:
4. The compound of claim 3 , wherein NBu 4 is any other counterion.
5. The compound of claim 3 , comprising L, D, or L and D stereoisomers of cysteine.
6. A glucose sensor comprising the compound of claim 1 .
7. The glucose sensor of claim 6 , further comprising a quencher moiety.
8. The glucose sensor of claim 7 , wherein said quencher moiety comprises boronic acid.
9. The glucose sensor of claim 8 , wherein said boronic acid quencher is 3,3′-oBBV.
10. A method of making the compound of claim 1 , comprising the steps of:
wherein:
R 2 is
R 3 is —(CH 2 ) n —A − M + ,
wherein n is 1-4,
wherein A − is an anionic group selected from the group consisting of SO 3 − ,
HPO 3 − , CO 2 − and
and
wherein M + is a cationic group selected from the group consisting of H + , an alkali metal ion, Li + , Na + , K + , Rb + , Cs + , Fr + , an onium ion and NR 4 + , wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
R 4 is
R 5 is selected from the group consisting of
wherein n is equal to 1-10, n′ is equal to 2-4 and Y is selected from the group consisting of NH and O;
R 6 is selected from the group consisting of NHR 7 , OR 7 and CO 2 H;
R 7 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl, acrylamido and methacrylamido; and
Z is an amino protecting group selected from the group consisting of Phthalimido, Boc and Fmoc.
11. A method of making the compound of claim 2 , comprising the steps of:
wherein:
R 3 is —(CH 2 ) n —A − M + ,
wherein n is 1-4,
wherein A − is an anionic group selected from the group consisting of SO 3 − ,
HPO 3 − , CO 2 − and
and
wherein M + is a cationic group selected from the group consisting of H + , an alkali metal ion, Li + , Na + , K + , Rb + , Cs + , Fr + , an onium ion and NR 4 + , wherein R is selected from the group consisting of alkyl, alkylaryl and aromatic groups);
R 8 is selected from the group consisting of
wherein n is equal to 1-10, n′ is equal to 2-4;
R 9 is selected from the group consisting of NHR 10 , OR 10 and CO 2 H; and
R 10 is H or an ethylenically unsaturated group selected from the group consisting of methacryloyl, acryloyl, styryl, acrylamido and methacrylamido.
12. A method of making the compound of claim 3 , comprising the steps of making HPTS-CysOH as follows; and
making HPTS-Cys-MA as follows:
13. A method of making the compound of claim 3 , comprising the steps of:
making TBCys as follows:
making Phth acid as follows:
making Phth MA as follows:
making AminoCysMA as follows:
and
making HPTS-Cys-MA as follows: