Selective tumor cell death induced by irradiated riboflavin through recognizing DNA G–T mismatch

Abstract

Riboflavin (vitamin B2) has been thought to be a promising antitumoral agent in photodynamic therapy, though the further application of the method was limited by the unclear molecular mechanism. Our work reveals that riboflavin was able to recognize G–T mismatch specifically and induce single-strand breaks in duplex DNA targets efficiently under irradiation. In the presence of riboflavin, the photo-irradiation could induce the death of tumor cells that are defective in mismatch repair system selectively, highlighting the G–T mismatch as potential drug target for tumor cells. Moreover, riboflavin is a promising leading compound for further drug design due to its inherent specific recognition of the G–T mismatch.

Ultrasensitive recognition of AP sites in DNA at the single-cell level: one molecular rotor sequentially self-regulated to form multiple different stable conformations

“…This process enables the AP site to activate the recognition reaction-specically, the hydrolysis reaction of the BMN-Fluors (Scheme S1 †). 1,2,9,10,[21][22][23]29 Then, to obtain a high-delity recognition signal, we introduced ethenyl as a linker of BMN-Fluors to self-regulate their conformations sequentially and thus form different stable states in the different cavity sizes of the AP sites. These different molecular stable conformations possess different HOMO-LUMO gaps, which enable the emission of different types of uorescence signals.…”

“…AP sites possess a special structure and reactivities that can spontaneously induce some chemical reactions in living biological systems. 9,10 Thus, developing active substrate molecules that can take part in the relevant chemical reactions induced by the AP site is immensely conducive for such site-specic recognition in a DNA sequence. 11,12 To date, combined with nuclear magnetic resonance (NMR) spectrometry, 13,14 mass spectrometry 15,16 and optical techniques, [17][18][19][20] some substrate molecules have been successfully implemented for quantifying AP sites in DNA.…”

Visible Light Photochemical Reactions for Nucleic Acid-Based Technologies

“…This iridium(III) complex could be effectively used for DNA photocleavage through the photoproduction of H 2 O 2 , single oxygen, and PET with nucleobases. Selective DNA cleavage and tumor cell death were studied by Wang, Jiang, and Tang in 2017 using riboflavin (15, vitamin B2) irradiation (Figure 7) [39]. Riboflavin is an essential natural photosensitizer and a key molecule for redox chemistry in enzyme activity.…”

“…Selective DNA cleavage and tumor cell death were studied by Wang, Jiang, and Tang in 2017 using riboflavin ( 15 , vitamin B2) irradiation ( Figure 7 ) [ 39 ]. Riboflavin is an essential natural photosensitizer and a key molecule for redox chemistry in enzyme activity.…”

“…Ru complex (Figure 5) ADA-AN -PDT with visible light -Water-soluble [35] Ir complex (Figure 6) CPIP -G-A DNA base pair triggered PET [37] Riboflavin (Figure 7) -Selective DNA photocleavage of the G-T mismatch [39]…”