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US 12,692,532 B2Granted
Compounds and methods for amine oxidase imaging
AssigneeETH Zurich
InventorsMatthew Ronald Aronoff, Helma Wennemers
Life of this patent
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Abstract
The invention pertains to a functionalizable and enzyme-activatable fluorescent probe and methods for monitoring the activity of amine oxidases. Amine oxidases catalyze the oxidative deamination, e.g. of the ε-amine of a lysine to an aldehyde which in turn can form covalent bonds with neighboring side chains, e.g. in the context of collagen cross-linking. Amine oxidase activity can be correlated with collagen-associated diseases including pulmonary and hepatic fibrosis, cardiomyopathy and tumor metastasis.
Claims19
A compound according to Formula I
- wherein
- a and b are independently an integer from 0 to 10;
- A is a structure selected from the group consisting of
- R3 and R4 are independently selected from the group consisting of
- NHR9′, —OR9′, SR9′,
- linear or branched, substituted or non-substituted (C1-10)alkyl, (C2-10)alkenyl and (C2-10)alkynyl, or substituted or non-substituted carbocycle selected from the group consisting of (C3-10)carbocycle;
- substituted or non-substituted triphenylphosphine connected via the phosphorous;
- N-maleimidyl;
- and
- halogens, or one of R3 or R4 is a proteinogenic amino acid, a non-proteinogenic amino acid or a peptide, and the other of R3 or R4 is a halogen;
- L is absent or a linker;
- X, Y and Z are independently selected from the group consisting of O, N and S;
- R9′ is selected from the group consisting of
- hydrogen;
- linear or branched, substituted or non-substituted, optionally sulfonated, (C1-10)alkyl, (C2-10)alkenyl, or (C2-10)alkynyl;
- linear or branched, substituted or non-substituted (C1-20)alkyl ether, (C2-10)alkenyl ether, (C2-10)alkynyl ether, or (C4-10)carbocyclic ether;
- substituted or non-substituted carbocycle selected from the group consisting of (C3-10)carbocycle;
- substituted or non-substituted triphenylphosphine connected via the phosphorous;
- substituted or non-substituted (C3-6)heterocycle and (C7-C10)carbo- or hetero-bicycle having 1 to 3 heteroatoms each independently selected from N, O and S;
- a proteinogenic amino acid or non-proteinogenic amino acid;
- a peptide or a peptide comprising 1 to 2000 amino acids;
- a collagen peptide, fibronectin peptide, fibrillin peptide, elastin peptide, or an RGD (arginylglycylaspartic acid) peptide;
- and
- an antibody;
- R9 is selected from residues defined for R9′ and is further selected from the group consisting of
- azide, N-maleimidyl, —NH2, —OH and —SH2;
- R9″ is selected from the group consisting of
- halogen, substituted or non-substituted triphenylphosphine connected via the phosphorous, azide, —SR10,
- R10 is selected from the group consisting of
- linear or branched, substituted or non-substituted (C1-10)alkyl, (C2-10)alkenyl, or (C2-10)alkynyl;
- and
- linear or branched, substituted or non-substituted (C1-20)alkyl ether, (C2-10)alkenyl ether, (C2-10)alkynyl ether, or (C4-10)carbocyclic ether;
- R5 is selected from the group consisting of
- hydrogen or —OH;
- and
- halogens;
- R6 and R8 are independently selected from the group consisting of hydrogen, —OH, and halogen;
- and
- R7 is each independently selected from the group consisting of
- hydrogen;
- linear or branched, substituted or non-substituted (C1-10)alkyl, (C2-10) alkenyl, or (C2-10)alkynyl;
- linear or branched, substituted or non-substituted (C1-20)alkyl ether, (C2-10)alkenyl ether, (C2-10)alkynyl ether, or (C4-10)carbocyclic ether;
- —N2 forming an azide with the nitrogen atom of A;
- and
- tert-Butyloxycarbonyl (Boc), 9-fluorenylmethoxycarbonyl (Fmoc), benzyloxycarbonyl(Cbz), acetyl (Ac), trifluoroacetic acid (TFA), phthalimide, benzyl (Bn), triphenylmethyl (Tr), benzylidene, or para-toluenesulfonyl (Ts);
- and salts and solvates thereof.
43 more elements
Dependencies are inferred from the claim text.