Sequence-specific recognition, photocrosslinking and cleavage of the DNA double helix by an oligo-(α]-thymidylate covalently linked to an azidoproflavine derivative
Open Access
- 12 October 1987
- journal article
- research article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 15 (19), 7749-7760
- https://doi.org/10.1093/nar/15.19.7749
Abstract
A 3-azidoproflavine derivative was covalently linked to the 5'-end of an octathymidylate synthesized with the [α]-anomers of the nucleoside. Two target nucleic acids were used for this substituted oligo-[α]-thymidylate: a 27-mer single-stranded DNA fragment containing an octadeoxyadenylate sequence and a 27-mer duplex containing eight contiguous A.T base pairs with all ade-nines on the same strand. Upon visible light irradiation the octa-[α]-thymi-dylate was photocrosslinked to the single-stranded 27-tner. Chain breaks were induced at the crossllnked sites upon piperidine treatment. From the location of the cleavage sites on the 27-mer sequence it was concluded that a triple helix was formed by the azidoproflavine-substltuted oligo-[α]-thymidylate with its complementary oligodeoxyadenylate sequence. When the 27-mer duplex was U3ed as a substrate cleavage 3ites were observed on both strands after piperidine treatment of the irradiated sample. They were located at well defined positions which indicated that the octathymidylate was bound to the (dA)8.(dT)8 sequence in a parallel orientation with respect to the (dA)8-con-taining strand. Specific binding of the [α]-octathymidylate involved local triple strand formation with the duplex (dA)8.(dT)s sequence. This result shows that it is possible to synthesize sequence-specific molecules which specifically bind oligopurlne-oligopyrlmidine sequences in double-stranded DNA via recognition of the major groove hydrogen bonding sites of the purines.Keywords
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