Photogeneration of highly electrophilic benzoylketene from dibenzoyldiazomethane in aqueous solvents: Reaction with amino acids and DNA cleavage

Mechanistic Studies on Photoinduced Cross-Linking and Specific Cleavage at Guanine by Dibenzoyldiazomethane-Oligodeoxynucleotide Conjugate

“…In aqueous solvents, photoirradiation of 1a with guanosine derivative 5 produced neither N-2 nor N7 acylated product probably due to the quenching of photogenerated BK by solvent water. We separately confirmed the formation of BK under the conditions by trapping with much stronger nucleophiles such as aliphatic amines (21). Therefore, the cross-linking between G 16 and photogenerated benzoyl ketene can occur only when DBDM is placed in the close vicinity to the target G residue.…”

“…experiment, the above photoirradiated mixture was heated with piperidine and analyzed by electrophoresis on denatured sequencing gel, showing a highly selective and strong cleavage band at G 16 (Fig. 5, lane 3) together with very weak cleavage bands at G 19 and G 21 . These observations are consistent with earlier reported results (22).…”

“…Thus, the postactivation of an electrophile precursor by a phototriggered process would be highly attractive for sequencespecific DNA alkylation by designed ODN 2 conjugates. Toward this end, we have designed a novel photoinducible DNA-alkylating agent that can generate a strong electrophile after complexation with the target sequence triggered by photoirradiation and alkylate guanine base at the close vicinity (21)(22)(23). Our attention has been focused on the compounds having dibenzoyldiazomethane (DBDM) 1a as a chromophore, which produces highly electrophilic benzoyl ketene (BK) 2 via photochemical Wolff rearrangement (21)(22)(23).…”

“…Toward this end, we have designed a novel photoinducible DNA-alkylating agent that can generate a strong electrophile after complexation with the target sequence triggered by photoirradiation and alkylate guanine base at the close vicinity (21)(22)(23). Our attention has been focused on the compounds having dibenzoyldiazomethane (DBDM) 1a as a chromophore, which produces highly electrophilic benzoyl ketene (BK) 2 via photochemical Wolff rearrangement (21)(22)(23). We previously observed that DNA cleavage occurred selectively at guanine (G) residues when DNA was photoirradiated in the presence of water-soluble monomer DBDM 1b followed by hot piperidine treatment (21,22).…”

“…Our attention has been focused on the compounds having dibenzoyldiazomethane (DBDM) 1a as a chromophore, which produces highly electrophilic benzoyl ketene (BK) 2 via photochemical Wolff rearrangement (21)(22)(23). We previously observed that DNA cleavage occurred selectively at guanine (G) residues when DNA was photoirradiated in the presence of water-soluble monomer DBDM 1b followed by hot piperidine treatment (21,22). G-selective DNA cleavage may also occur by singlet oxygen mediated mechanism (24)(25)(26)(27) or by one-electron oxidation of DNA (28)(29)(30)(31)(32)(33)(34)(35).…”