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

Ward, Jonathan S. and Palo, Alice De and Aucott, Benjamin J. and Moir, James W. B. and Lynam, Jason M. and Fairlamb, Ian J. S. (2019) A biotin-conjugated photo-activated CO-releasing molecule (biotinCORM) : efficient CO-release from an avidin–biotinCORM protein adduct. Dalton Transactions, 48 (43). pp. 16233-16241. ISSN 1477-9226

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.