Enzymatic triggering of C–ON bond homolysis of alkoxyamines. Issue 21 (26th September 2019)

• Record Type: Journal Article
• Authors: Audran, Gérard; Bosco, Lionel; Brémond, Paul; Jugniot, Natacha; Marque, Sylvain R. A.; Massot, Philippe; Mellet, Philippe; Moussounda Moussounda Koumba, Tataye; Parzy, Elodie; Rivot, Angélique; Thiaudière, Eric; Voisin, Pierre; Wedl, Carina; Yamasaki, Toshihide
• Is Part Of: Organic chemistry frontiers. Volume 6:Issue 21(2019)
• Page Start: 3663
• Page End: 3672
• Publication Date: 2019-09-26
• Subjects: Chemistry, Organic -- Periodicals; 547.005
• DOI: 10.1039/c9qo00899c
• Languages: English
• ISSNs: 2052-4110

Abstract

Abstract : Alkoxyamine 1 is selectively hydrolyzed by chymotrypsin and substilisin A into alkoxyamine 2H+ for which C–ON bond homolysis occurred with a 4-fold increase in rate constants compared to 1 while non-specific proteases had no effect. Abstract : Alkoxyamine 1 is selectively hydrolyzed by chymotrypsin and substilisin A into alkoxyamine 2H+ for which C–ON bond homolysis occurred with a 4-fold increase in rate constants compared to 1 while non-specific proteases had no effect. This highlights the triggering effect of enzymes. This is a proof of concept for a theranostic approach for treating solid tumors using enzyme-activated alkoxyamines releasing a cytotoxic alkyl radical and a stable nitroxide as a contrast agent for Overhauser-enhanced MRI.