Towards aspirin-inspired self-immolating molecules which target the cyclooxygenases
- Author(s): Drake, CR
- Estévez-Salmerón, L
- Gascard, P
- Shen, Y
- Tlsty, TD
- Jones, EF
- et al.
Published Web Locationhttps://doi.org/10.1039/c5ob01805f
© 2015 The Royal Society of Chemistry. 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.
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