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US 12,173,350 B2Granted
Chemiluminescent probes for imaging/detection of proteases
AssigneeRamot at Tel-Aviv University Ltd.
InventorsDoron Shabat, Michal Eli Roth-Konforti
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Abstract
The present invention provides turn-ON dioxetane-based chemiluminescence probes based on the Schapp's adamantylidene-dioxetane probe, which are capable of detecting or imaging, more specifically, determining the presence, or measuring the level, of proteases, as well as compositions and uses thereof.
Claims22
A compound of the formula Ia or Ib:
- wherein
- R1 is selected from the group consisting of a linear or branched (C1-C18)alkyl, or (C3-C7)cycloalkyl;
- R2 and R3 each independently is selected from the group consisting of a branched (C3-C18)alkyl and (C3-C7)cycloalkyl, or R2 and R3 together with the carbon atom to which they are attached form a fused, spiro or bridged cyclic or polycyclic ring;
- R4 is a group of the formula:
- R5 is H, or halogen attached either ortho or para to the —O—R4 group;
- A is a π* acceptor group of the formula —CH═CH-E, attached either ortho or para to the —O—R4 group, wherein E is —CN, —COOH, —COO(C1-C18)alkyl, 4-pyridinyl, methylpyridinium-4-yl, 3,3-dimethyl-3H-indolyl, or 1,3,3-trimethyl-3H-indol-1-ium-2-yl;
- Pep1 is a protease cleavable peptide moiety consisting of at least two amino acid residues and linked via a carboxylic group thereof to the aniline group, wherein said peptide moiety is protected or linked through an amino group thereof to a polyethylene glycol (PEG)-containing group;
- L is absent;
- and
- Pep2 is absent.
7 more elements
A compound of the formula Ia or Ib:
- wherein
- R1 is selected from a linear or branched (C1-C18)alkyl, or (C3-C7)cycloalkyl;
- R2 and R3 each independently is selected from the group consisting of a branched (C3-C18)alkyl and (C3-C7)cycloalkyl, or R2 and R3 together with the carbon atom to which they are attached form a fused, spiro or bridged cyclic or polycyclic ring;
- R4 is a group of the formula:
- R5 is H, or halogen attached either ortho or para to the —O—R4 group;
- A is a π* acceptor group of the formula —CH═CH-E, attached either ortho or para to the —O—R4 group, wherein E is —CN, —COOH, —COO(C1-C18)alkyl, 4-pyridinyl, methylpyridinium-4-yl, 3,3-dimethyl-3H-indolyl, or 1,3,3-trimethyl-3H-indol-1-ium-2-yl;
- Pep1 is a protease cleavable peptide moiety consisting of at least two amino acid residues and linked via a carboxylic group thereof to the aniline group;
- L is a linker linked to Pep1 via an amide bond through either a carboxyl or amino group of Pep1;
- and
- Pep2 is a cell-penetrating peptide moiety linked to L through a thiol group thereof.
7 more elements
Dependencies are inferred from the claim text.