Light-mediated double-strand DNA cleavage by an alkyldicobalamin

Abstract

Agents that cause double-strand breaks (DSBs) of DNA via radical formation have been demonstrated to be effective in treating cancer because DSBs result in cellular apoptosis. Light-responsive agents for the treatment of cancer have been of interest for decades because they afford the ability to spatially control chemical reactions limiting the effects by controlling the area of illumination. Alkylcobalamins, which are structurally related to Vitamin B₁₂ (B₁₂), produce radicals with very high quantum yields when illuminated with green light (approximately 530 nm). Cancerous cells uptake alkylcobalamins to a greater extent than healthy cells because these rapidly dividing cells have an increased demand for B₁₂. Tethering two cobalamins with a propyl group results in a complex that causes true DNA DSBs in a light-mediated manner.