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Journal of Nucleic Acids
Volume 2010, Article ID 523498, 7 pages
Research Article

Structural Determinants of Photoreactivity of Triplex Forming Oligonucleotides Conjugated to Psoralens

1Department of Dermatology, University of California at San Francisco, San Francisco, CA 94121 , USA
2Dermatology Research Unit, San Francisco VA Medical Center, 4150 Clement Street, San Francisco, CA 94121, USA

Received 15 May 2010; Accepted 3 June 2010

Academic Editor: Ashis Basu

Copyright © 2010 Rajagopal Krishnan and Dennis H. Oh. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Triplex-forming oligonucleotides (TFOs) with both DNA and -O-methyl RNA backbones can direct psoralen photoadducts to specific DNA sequences. However, the functional consequences of these differing structures on psoralen photoreactivity are unknown. We designed TFO sequences with DNA and -O-methyl RNA backbones conjugated to psoralen by 2-carbon linkers and examined their ability to bind and target damage to model DNA duplexes corresponding to sequences within the human HPRT gene. While TFO binding affinity was not dramatically affected by the type of backbone, psoralen photoreactivity was completely abrogated by the -O-methyl RNA backbone. Photoreactivity was restored when the psoralen was conjugated to the RNA TFO via a 6-carbon linker. In contrast to the B-form DNA of triplexes formed by DNA TFOs, the CD spectra of triplexes formed with -O-methyl RNA TFOs exhibited features of A-form DNA. These results indicate that -O-methyl RNA TFOs induce a partial B-to-A transition in their target DNA sequences which may impair the photoreactivity of a conjugated psoralen and suggest that optimal design of TFOs to target DNA damage may require a balance between binding ability and drug reactivity.