Towards aspirin-inspired self-immolating molecules which target the cyclooxygenasesElectronic supplementary information (ESI) available: Experimental details, HPLC traces, UV-Vis spectra and NMR spectra. See DOI: 10.1039/c5ob01805f

Cyclooxygenases (COXs) are enzymes that play a vital role in the inflammatory cascade through the generation of prostaglandins. Their over-expression has been implicated in numerous diseases. In particular, over-expression of COX-2 has been shown to be a predictive biomarker for progression of pre-m...

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Main Authors: Drake, Christopher R, Estévez-Salmerón, Luis, Gascard, Philippe, Shen, Yang, Tlsty, Thea D, Jones, Ella F
Format: Article
Language:English
Online Access:Get full text
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Summary:Cyclooxygenases (COXs) are enzymes that play a vital role in the inflammatory cascade through the generation of prostaglandins. Their over-expression has been implicated in numerous diseases. In particular, over-expression of COX-2 has been shown to be a predictive biomarker for progression of pre-malignant lesions towards invasive cancer in various tissues. This makes the early detection of COX-2 expressing lesions of high clinical relevance. Herein we describe the development of the first self-immolating trigger which targets COXs. We incorporated our trigger design into 2 activatable fluorogenic probes and demonstrated COX-specific activation in vitro . Experimental data revealed probe activation was likely caused by solvent-exposed amino acids on the surface of the COXs. Overall, the probes reported here mark the first step towards developing self-immolating imaging/therapeutic agents targeted to specific COXs. Cyclooxygenase specific self-immolative triggers and their use in activatable fluorescent probes are reported.
ISSN:1477-0520
1477-0539
DOI:10.1039/c5ob01805f