Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The self-immolative spacer para-aminobenzyl alcohol (PABA) was used as a key component in the design of new protease-sensitive fluorogenic probes whose parent phenol-based fluorophore is released through an enzyme-initiated domino reaction. First, the conjugation of the phenylacetyl moiety to 7-hydroxycoumarin (umbelliferone) and 7-hydroxy-9 H-(9,9-dimethylacridin-2-one) (DAO) by means of the heterobifunctional PABA linker has led to pro-fluorophores 6a and 6d whose enzyme activation by penicillin amidase was demonstrated. The second part of this study was devoted to the extension of this latent fluorophore strategy to the caspase-3 protease, a key mediator of apoptosis in mammalian cells. Fluorogenic caspase-3 substrates 11 and 13 derived from umbelliferone and DAO, respectively, were prepared. It was demonstrated that pro-fluorophore 11 is a sensitive fluorimetric reagent for the detection of this cysteine protease. Furthermore, in vitro assays with fluorogenic probe 13 showed a deleterious effect of biological thiols on fluorescence of the released acridinone fluorophore DAO that, to our knowledge, had not been reported until now.
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PMID:Latent fluorophores based on a self-immolative linker strategy and suitable for protease sensing. 1864 65

A new generation of dioxetane-based chemiluminescent substrates suitable for detecting protease activities is described. Our strategy involves the use of a self-cleavable spacer as the key molecular component of these protease-sensitive chemiluminescent probes. Among the assayed strategies, the PABA (para-aminobenzylic alcohol) linker associated with an ether linkage enables the release of the light-emitting phenolic 1,2-dioxetane moiety through an enzyme-initiated domino reaction. To validate this strategy, two proteolytic enzymes were chosen: penicillin amidase and caspase-3, and the corresponding self-cleavable chemiluminescent substrates were synthesised. Their evaluation using an in vitro assay has enabled us to prove the decomposition of the linker under physiological conditions and the selectivity for the targeted enzyme.
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PMID:Self-cleavable chemiluminescent probes suitable for protease sensing. 1958 5