Fluorescent probe for detecting carboxypeptidase activity
AssigneeThe University of Tokyo
InventorsYasuteru Urano, Mako Kamiya, Minoru Kawatani, Hirohisa Iwaki, Kyoko Yamamoto, Haruki Kume, Daisuke Yamada
Life of this patent
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Abstract
A fluorescent probe can be used to detect and visualize carboxypeptidase activity with high sensitivity. The fluorescent probe has, as a base nucleus, a fluorescent skeleton that functions in the visible light region, and makes carboxypeptidase activity detectable and visible, for example, within a cell or clinical specimen, with high sensitivity.
Claims14
A compound represented by the following general formula (I) or a salt thereof:
- wherein
- R1 represents a hydrogen atom or one to three monovalent substituent groups present on a benzene ring, which are the same or different;
- R2 represents a monovalent substituent group present on a benzene ring;
- R3 and R4 are, each independently, a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or a halogen atom;
- R5 and R6 are, each independently, a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or a halogen atom;
- L represents an amino acid residue;
- X is selected from an oxygen atom, Si(Ra)(Rb), C(Ra)(Rb), Ge(Ra)(Rb), P(═O)Rc or Se
- where:
- Ra and Rb are, each independently, an alkyl group having 1 to 6 carbon atoms or an aryl group optionally being substituted, and Rc is an alkyl group having 1 to 6 carbon atoms or a phenyl group optionally being substituted;
- Y and Z are selected from a pair of (O, OH), (NR7R8, NR9R10), and (O, NR9R10) where:
- R7 and R8 are, each independently, a hydrogen atom or an alkyl group having 1 to 3 carbon atoms;
- R7 and R8 together optionally form a 4-7 membered heterocyclyl containing a nitrogen atom to which R7 and R8 are bonded;
- R7 or R8, or both R7 and R8, together with R3 and/or R5, respectively, optionally form a 5-7 membered heterocyclyl or heteroaryl containing a nitrogen atom to which R7 and/or R8 are bonded, and optionally contain from one to three heteroatoms selected from the group consisting of an oxygen atom, nitrogen atom, and sulfur atom as ring-constituting members, and the heterocyclyl or heteroaryl is optionally substituted by alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, alkynyl having 2 to 6 carbon atoms, aralkyl group having 6 to 10 carbon atoms, or alkyl-substituted alkenyl group having 6 to 10 carbon atoms;
- R9 and R10 are, each independently, a hydrogen atom or an alkyl group having 1 to 3 carbon atoms;
- R9 and R10 together optionally form a 4-7 membered heterocyclyl containing a nitrogen atom to which R9 and R10 are bonded;
- R9 or R10, or both R9 and R10, together with R4 and/or R6, respectively, optionally form a 5-7 membered heterocyclyl or heteroaryl containing a nitrogen atom to which R9 and/or R10 are bonded, and optionally contain from one to three heteroatoms selected from the group consisting of an oxygen atom, nitrogen atom, and sulfur atom as ring-constituting members, and the heterocyclyl or heteroaryl is optionally substituted by alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 6 carbon atoms, alkynyl having 2 to 6 carbon atoms, aralkyl group having 6 to 10 carbon atoms, or alkyl-substituted alkenyl group having 6 to 10 carbon atoms;
- and
- when Y and Z are O and OH, respectively, and when a monovalent substituent group present on a benzene ring of R2 is a carboxyl group, Y and Z are optionally acetylated.
A compound represented by the following general formula (V) or salt thereof:
- wherein
- R1 represents a hydrogen atom or one to three monovalent substituent groups present on a benzene ring, which are the same or different;
- R3 and R4 are, each independently, a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or a halogen atom;
- R5 and R6 are, each independently, a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or a halogen atom;
- L represents an amino acid residue;
- X is selected from an oxygen atom, Si(Ra)(Rb), C(Ra)(Rb), Ge(Ra)(Rb), P(═O)Rc or Se
- where:
- Ra and Rb are, each independently, an alkyl group having 1 to 6 carbon atoms or an aryl group optionally being substituted, and Rc is an alkyl group having 1 to 6 carbon atoms or a phenyl group optionally being substituted;
- wherein Ac represents an acetyl group.
A compound selected from the group consisting of the following formulas, or a salt thereof:
- wherein R2 is CH2CH2COOH or CH2CH2CH2CH2NH2.
Dependencies are inferred from the claim text.