Photo-cross-linking reactions in RNA–DNA heteroduplexes using photoreactive DNA incorporated with diazirine and aryl azide warheads

Abstract

Utilizing photoreactive oligodeoxyribonucleotides (ODNs) presents a promising avenue for significantly enhancing antisense effects with high spatiotemporal resolution. This enhancement arises from the increased stability of RNA–DNA heteroduplexes achieved through photo-cross-linking with complementary RNAs upon light illumination. In this study, we propose a post-introduction approach for preparing ODNs incorporating diazirine and aryl azide warheads, employing 2′-amino-2′-deoxyuridine. We investigate the photo-cross-linking efficiencies, rates, and nucleobase preferences of these photoreactive ODNs when paired with their complementary RNAs.