A biotin-conjugated photo-activated CO-releasing molecule (biotinCORM): efficient CO-release from an avidin–biotinCORM protein adduct

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.