Bioorthogonal oxime ligation of a Mo(CO)4(N-N) CO-releasing molecule (CORM) to a TGF β-binding peptide

Carbon monoxide is now well-established as an endogenously produced gasotransmitter in humans. To utilizes its spectrum of biological activity for therapeutic purposes, solid storage forms such as metal carbonyl complexes have to be used for easy handling and targeted delivery to the body. Thus, in the present work, a [Mo(CO)(4)(bpy(CH3,CHO))] complex with an aldehyde group in a periphetal position on the 2,2'-bipyridine (bpy) ligand was coupled to a bioactive transforming growth factor (TGF) beta-targeting peptide N-terminally functionalized with aminoxy acetic acid using the bioorthogonal and catalyst-free oxime ligation. CO release studies with the myoglobin assay as well as UV/Vis and IR spectroscopy showed the molybdenum tetracarbonyl moiety to slowly liberate carbon monoxide upon incubation in buffer in the dark. In addition, photoactivation at 468 nm with a LED array resulted in a significantly accelerated release of carbon monoxide, thus establishing this peptide bioconjugate as a new photoactivatable CO-releasing molecule (PhotoCORM) with a red-shifted excitation wavelength for better tissue penetration. (C) 2012 Elsevier B.V. All rights reserved.