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US 8,664,009 B2Granted
Arsenical fluorescent agents and assays
AssigneeSRI International
InventorsLaura Ellen Downs Beaulieu, Mary J. Tanga
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Abstract
The invention provides methods and compositions for labeling dithiol-containing analytes.
Claims19
A method of diagnosing a trypanasomatid infection in a patient by detecting a dicysteine trypanathione, comprising the steps of:
- (a) contacting a sample of the patient with an arsenical fluorescent dye that exhibits a detectable increase or shift in fluorescence when the arsenic of the dye reacts with the cysteines of the trypanathione;
- and
- (b) detecting the increase or shift in fluorescence as an indication of the presence of the trypanathione and the trypanasomatid infection;
- wherein the dye is a substituted, optionally hydro-, optionally hetero-, monoarsenical anthracene compound comprising a 4′ rotation blocking group and a 5′ arsenic, and that exhibits a detectable increase or shift in fluorescence when the arsenic reacts with two thiols of a rotation-blocking binding target molecule, the compound having the structure I:
- wherein:
- R1 is O, S, NRα, or CRα2;
- R2 is C or N;
- R3 is optionally substituted-, optionally hetero-alkyl, optionally substituted-, optionally hetero-alkenyl, optionally substituted-, optionally hetero-alkynyl, optionally substituted-, optionally hetero-aryl, or optionally substituted-, optionally hetero-alkoxy;
- R4 and R5 are independently carbonyl, carbonothioyl, NRα2, ORα, or SRα;
- R6 and R7 are Rα, halide, ORα, NRα2, ORα, SRα, or nitro (—NO2);
- R8 and R9 are Rα, halide, ORα, NRα2, ORα, SRα, or nitro (—NO2);
- R10 is a rotational blocking group;
- R11 is an arsenic protecting group displaced by reaction of the arsenic with the thiols of the target molecule;
- Rα groups are independently H, optionally substituted-, optionally hetero-alkyl, optionally substituted-, optionally hetero-alkenyl, optionally substituted-, optionally hetero-alkynyl, optionally substituted-, optionally hetero-aryl, or optionally substituted-, optionally hetero-alkoxy;
- wherein one or more of the pairs R4-R6, R6-R8, R5-R7, and R7-R9 may be covalently joined in one or more rings;
- and tautomers, anhydrides and salts of the compound.
13 more elements
Dependencies are inferred from the claim text.