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Recognition of all four base pairs of double-helical DNA by triple-helix formation: design of nonnatural deoxyribonucleosides for pyrimidine•purine base pair binding

Griffin, Linda C. and Kiessling, Laura L. and Beal, Peter A. and Gillespie, Paul and Dervan, Peter B. (1992) Recognition of all four base pairs of double-helical DNA by triple-helix formation: design of nonnatural deoxyribonucleosides for pyrimidine•purine base pair binding. Journal of the American Chemical Society, 114 (21). pp. 7976-7982. ISSN 0002-7863. doi:10.1021/ja00047a003. https://resolver.caltech.edu/CaltechAUTHORS:20160510-141139929

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Abstract

The sequence-specific recognition of double-helical DNA by oligonucleotide-directed triple-helix formation is limited mostly to purine tracts. Design leads that could expand the recognition code to all four Watson-Crick base pairs would provide one step toward a general solution targeting single sites in megabase size DNA. The nonnatural deoxyribonucleoside 1-(2-deoxy-beta-D-ribofuranosyl)-4-(3-benzamidophenyl)imidazole (D3) was synthesized in four steps and incorporated by automated methods into pyrimidine oligodeoxyribonucleotides. Within a pyrimidine oligonucleotide, D3 binds pyrimidine.purine base pairs with higher affinity than it binds purine.pyrimidine base pairs. From affinity-cleaving analysis, the stabilities of base triplets decrease in the order D3.TA is similar to D3.CG > D3.AT > D3.GC. Such specificity allows binding by triple-helix formation at an 18 base pair site in SV40 DNA containing all four base pairs at physiologically relevant pH and temperature. The stabilities of these novel triplets may be an example of shape-selective recognition of CG and TA Watson-Crick base pairs in the major groove.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1021/ja00047a003DOIArticle
http://pubs.acs.org/doi/abs/10.1021/ja00047a003PublisherArticle
ORCID:
AuthorORCID
Dervan, Peter B.0000-0001-8852-7306
Additional Information:© 1992 American Chemical Society. Received January 27, 1992. Publication Date: October 1992. We are grateful to the Office of Naval Research, the National Institutes of Health, and the Parsons Foundation for generous support and to the American Cancer Society for a fellowship to L.L.K. We thank Dr. Heinz Moser for helpful discussions.
Funders:
Funding AgencyGrant Number
Office of Naval Research (ONR)UNSPECIFIED
NIHUNSPECIFIED
Ralph M. Parsons FoundationUNSPECIFIED
American Cancer SocietyUNSPECIFIED
Issue or Number:21
DOI:10.1021/ja00047a003
Record Number:CaltechAUTHORS:20160510-141139929
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20160510-141139929
Official Citation:Recognition of all four base pairs of double-helical DNA by triple-helix formation: design of nonnatural deoxyribonucleosides for pyrimidine.cntdot.purine base pair binding Linda C. Griffin, Laura L. Kiessling, Peter A. Beal, Paul Gillespie, and Peter B. Dervan Journal of the American Chemical Society 1992 114 (21), 7976-7982 DOI: 10.1021/ja00047a003
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:66935
Collection:CaltechAUTHORS
Deposited By: Victoria Brennan
Deposited On:19 May 2016 17:23
Last Modified:11 Nov 2021 00:24

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