A biotin-conjugated photo-activated CO-releasing molecule (biotinCORM): efficient CO-release from an avidin–biotinCORM protein adduct. Issue 43 (10th October 2019)

• Record Type: Journal Article
• Authors: Ward, Jonathan S.; De Palo, Alice; Aucott, Benjamin J.; Moir, James W. B.; Lynam, Jason M.; Fairlamb, Ian J. S.
• Is Part Of: Dalton transactions. Volume 48:Issue 43(2019)
• Page Start: 16233
• Page End: 16241
• Publication Date: 2019-10-10
• Subjects: Chemistry, Inorganic -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Chemistry, Inorganic -- Periodicals; 546.05
• DOI: 10.1039/c9dt03429c
• Languages: English
• ISSNs: 1477-9226

Abstract

Abstract : A biotinylated carbon monoxide-releasing molecule (BiotinCORM) releases CO by photoirradiation at 400 nm; an avidin–biotinCORM adduct is an effective CO-releasing molecule. Abstract : Biotinylated pharmaceuticals are of great interest due to the strong interactions between biotinyl-functionality and streptavidin/avidin, which opens up avenues for efficient targeting and localisation. Three new carbon monoxide-releasing molecules (CO-RMs) have been synthesised and characterised using chemical and biological analysis. An alkyne-containing CO-RM 2 was found to be toxic to RAW 264.7 murine macrophages; and thus therapeutically viable CO-RM 1 was employed as the alkyne precursor for [3 + 2] cycloaddition chemistry enabling a new acid-containing CO-RM 4 and biotin-bioconugate-CO-RM (BiotinCORM 5 ) to be prepared. CO-RM 4 showed significantly improved solubility and BiotinCORM 5 acts as a photo-CO-RM. We have found that an avidin–CORM adduct of 5 is a CO-releasing protein, releasing CO on irradiation with light (400 nm). The avidin–biotinCORM adduct of 5 was found to have a binding energy of 10 kcal mol −1 .