Sequence-specific electron injection into DNA from an intermolecular electron donor

Abstract

Electron transfer in DNA has been intensively studied to elucidate its biological roles and for applications in bottom-up DNA nanotechnology. Recently, mechanisms of electron transfer to DNA have been investigated; however, most of the systems designed are intramolecular. Here, we synthesized pyrene-conjugated pyrrole-imidazole polyamides (PPIs) to achieve sequence-specific electron injection into DNA in an intermolecular fashion. Electron injection from PPIs into DNA was detected using 5-bromouracil as an electron acceptor. Twelve different 5-bromouracil-containing oligomers were synthesized to examine the electron-injection ability of PPI. Product analysis demonstrated that the electron transfer from PPIs was localized in a range of 8 bp from the binding site of the PPIs. These results demonstrate that PPIs can be a useful tool for sequence-specific electron injection.

Probing of G-Quadruplex Structures via Ligand-Sensitized Photochemical Reactions in BrU-Substituted DNA

“…Supplementary Fig. S4 ) 29 , 30 , 39 . Although a total yield of strand cleavage products obtained with M-1PY and M-2PY was comparable (5–7%), the distribution of cleavage sites revealed significant differences between these two ligands: for M-1PY, the principal cleavage sites originated from Br U17 and Br U18 ( loop 3 of the G4 structure), whereas in the case of M-2PY most cleavage was due to Br U residues of loop 1 and loop 2.…”

“…In addition, ligand-sensitized electron injection can be correlated to the ligand binding site in the DNA structure (“photofootprinting”). This technique, developed by Sugiyama’s group, has been successfully employed for detection of binding sites of pyrene-conjugated pyrrole–imidazole polyamides, a family of sequence-specific minor-groove binders 29 , 30 .…”

Photoreaction of DNA Containing 5‐Halouracil and its Products†

“…Pyrrole-imidazole polyamide, which is a groove binder, allows the molecular design of sequence-specific binding to DNA by changing the sequence of the constituent pyrroles and imidazoles (72). We used the reaction of Br U triggered by electron transfer to investigate the polyamide-binding sites on a DNA duplex (73,74). Because the polyamide itself cannot donate an electron to Br U, the conjugation of the polyamide to pyrene, which is an electron donor, is necessary (Fig.…”

UVA irradiation of BrU-substituted DNA in the presence of Hoechst 33258

“…Importantly, DNA cleavage did not occur in the absence of Hoechst 33258, suggesting that photo-induced electron transfer from Hoechst 33258 to Br U residues is indispensable for uracil-2yl radical formation, as reported previously. 18,19 The mapping of DNA cleavage sites on DNA1 is shown in Fig. 2(b).…”