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Structural Determinants of Photoreactivity of Triplex Forming Oligonucleotides Conjugated to Psoralens
Joint Authors
Krishnan, Rajagopal
Oh, Dennis H.
Source
Issue
Vol. 2010, Issue 2010 (31 Dec. 2010), pp.1-7, 7 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2010-07-25
Country of Publication
Egypt
No. of Pages
7
Main Subjects
Abstract EN
Triplex-forming oligonucleotides (TFOs) with both DNA and 2′-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 2′-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 2′-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 2′-O-methyl RNA TFOs exhibited features of A-form DNA.
These results indicate that 2′-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.
American Psychological Association (APA)
Krishnan, Rajagopal& Oh, Dennis H.. 2010. Structural Determinants of Photoreactivity of Triplex Forming Oligonucleotides Conjugated to Psoralens. Journal of Nucleic Acids،Vol. 2010, no. 2010, pp.1-7.
https://search.emarefa.net/detail/BIM-478432
Modern Language Association (MLA)
Krishnan, Rajagopal& Oh, Dennis H.. Structural Determinants of Photoreactivity of Triplex Forming Oligonucleotides Conjugated to Psoralens. Journal of Nucleic Acids No. 2010 (2010), pp.1-7.
https://search.emarefa.net/detail/BIM-478432
American Medical Association (AMA)
Krishnan, Rajagopal& Oh, Dennis H.. Structural Determinants of Photoreactivity of Triplex Forming Oligonucleotides Conjugated to Psoralens. Journal of Nucleic Acids. 2010. Vol. 2010, no. 2010, pp.1-7.
https://search.emarefa.net/detail/BIM-478432
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-478432