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US 9,696,310 B2Granted
Molecular sensor and methods of use thereof
AssigneeYeda Research and Development Co. Ltd.
InventorsDavid Margulies, Leila Motiei, Linor Unger
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Abstract
The present invention is directed to fluorescent molecular sensor based on Thiazole Orange for protein detection. Interaction of the protein target with the molecular sensors of this invention results in a significant increase in the fluorescence emission. The generation of light output signal enables one to detect protein biomarkers associated with different diseases or detecting the protein of interest also in living cells.
Claims50
A fluorescent monomolecular sensor, wherein said sensor is a Thiazole Orange-based protein identifier (TOPI) comprising a Thiazole Orange (TO) derivative and at least-one selective protein binders;
- wherein said sensor is represented by the structure of formula IX:
- wherein
- n, o, p and q are independently integers between 0 to 15;
- An− is a counter ion, selected from tosylate (p-toluenesulfonate;
- CH3C6H4SO3−), PF6−, CF3COO−, I−, Cl−, Br−, or F−;
- G1 and G2 are independently a bond, carbamate, amide, amine, C1-C12 alkyl amine, ester, ketone, O, N, S, carbonate, —O-alkyl-NH—, carbamoyl phosphate or phosphate;
- T1 is hydrogen or
- wherein, n′ is between 0 and 15;
- T2 is hydrogen or
- wherein q′ is between 0 and 15;
- V1, V1′, V2 and V2′ are independently a bond, a triazole, an amide [—C(O)NH or —NHC(O)], —C(O)O—, —OC(O)—, O, NH, N-alkyl, S, —PO4H—, C1-C12 alkyl ether, —NH-alkyl-NH—, —O-alkyl-NH—, —NH-alkyl-O— wherein said alkyl is optionally substituted and wherein said alkyl is optionally interrupted by an heteroatom consisting of O, N, P, S or combination thereof
- X1, X1′, X2 and X2′ are independently a bond or C1-C12alkyl, —C(O)NH—, —NHC(O), —C(O)O—, —OC(O)—, O, NH, N-alkyl, S, —PO4H—, C1-C12 alkyl ether, C1-C12-alkyl-NH, -alkyl-NHC(O)-alkyl, -alkyl-C(O)NH-alkyl, —NH-alkyl-NH—, —O-alkyl-NH—, —NH-alkyl-O— wherein said alkyl is optionally substituted and wherein said alkyl is optionally interrupted by an heteroatom consisting of O, N, P, S or combination thereof;
- L1, L1′, L2 and L2′ are independently a bond or C1-C12 alkyl, C(O), —C(O)NH—, —NHC(O)—, —C(O)O—, —OC(O)—, O, NH, C1-C12 N-alkyl, S, —PO4H, —PO4H—{[(CH2)yO]x}z—PO3H—, wherein y is between 1-5, x is between 1-10 and z is between 1-10, —PO4H—PEG, C1-C12 alkyl ether, C1-C12 alkylamine, C1-C12 alkyl-NH, —C(O)NH-alkyl, —NHC(O)-alkyl, NH-alkyl-NH—, —O— alkyl-NH—, —NH-alkyl-O—, wherein said alkyl is optionally substituted and wherein said alkyl is optionally interrupted by an heteroatom consisting of O, N, P, S or combination thereof;
- and
- R1, R1′, R2 and R2′ are independently hydrogen, halide, SO3−, CN, NO2, phosphate, SO3− or a selective protein binder;
- wherein at least one of R1, R1′, R2 and R2′ is a protein selective binder.
13 more elements
A compound, represented by the structure of formula IX:
- wherein
- n, o, p and q are independently integers between 0 to 15;
- An− is a counter ion, selected from tosylate (p-toluenesulfonate;
- CH3C6H4SO3−), PF6−, CF3COO−, I−, Cl−, Br−, or F−;
- G1 and G2 are independently a bond, carbamate, amide, amine, C1-C12 alkyl amine, ester, ketone, O, N, S, carbonate, —O-alkyl-NH—, carbamoyl phosphate or phosphate;
- T1 is hydrogen or
- wherein, n′ is between 0 and 15;
- T2 is hydrogen or
- wherein q′ is between 0 and 15;
- V1, V1′, V2 and V2′ are independently a bond, a triazole, an amide [—C(O)NH or —NHC(O)], —C(O)O—, —OC(O)—, O, NH, N-alkyl, S, —PO4H—, C1-C12 alkyl ether, —NH-alkyl-NH—, —O-alkyl-NH—, —NH-alkyl-O— wherein said alkyl is optionally substituted and wherein said alkyl is optionally interrupted by an heteroatom consisting of O, N, P, S or combination thereof
- X1, X1′, X2 and X2′ are independently a bond or C1-C12alkyl, —C(O)NH—, —NHC(O), —C(O)O—, —OC(O)—, O, NH, N-alkyl, S, —PO4H—, C1-C12 alkyl ether, C1-C12-alkyl-NH, -alkyl-NHC(O)-alkyl, -alkyl-C(O)NH-alkyl, —NH-alkyl-NH—, —O-alkyl-NH—, —NH-alkyl-O— wherein said alkyl is optionally substituted and wherein said alkyl is optionally interrupted by an heteroatom consisting of O, N, P, S or combination thereof;
- L1, L1′, L2 and L2′ are independently a bond or C1-C12 alkyl, C(O), —C(O)NH—, —NHC(O)—, —C(O)O—, —OC(O)—, O, NH, C1-C12 N-alkyl, S, —PO4H, —PO4H—{[(CH2)yO]x}z—PO3H—, wherein y is between 1-5, x is between 1-10 and z is between 1-10, —PO4H—PEG, C1-C12 alkyl ether, C1-C12 alkylamine, C1-C12 alkyl-NH, —C(O)NH-alkyl, —NHC(O)-alkyl, NH-alkyl-NH—, —O-alkyl-NH—, —NH-alkyl-O—, wherein said alkyl is optionally substituted and wherein said alkyl is optionally interrupted by an heteroatom consisting of O, N, P, S or combination thereof;
- and
- R1, R1′, R2 and R2′ are independently hydrogen, halide, SO3−, CN, NO2, phosphate, SO3− or a selective protein binder;
- wherein at least one of R1, R1′, R2 and R2′ is a protein selective binder.
12 more elements
Dependencies are inferred from the claim text.