Towards aspirin-inspired self-immolating molecules which target the cyclooxygenases. Issue 45 (24th September 2015)

• Record Type: Journal Article
• Authors: Drake, Christopher R.; Estévez-Salmerón, Luis; Gascard, Philippe; Shen, Yang; Tlsty, Thea D.; Jones, Ella F.
• Is Part Of: Organic & biomolecular chemistry. Volume 13:Issue 45(2015)
• Page Start: 11078
• Page End: 11086
• Publication Date: 2015-09-24
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/c5ob01805f
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : Cyclooxygenase specific self-immolative triggers and their use in activatable fluorescent probes are reported. Abstract : 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.