This Article Full Text Full Text (PDF) All Versions of this Article: biophysj.106.084137v1 91/7/2552    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kan, L.-s. Articles by Huang, D.-H. Search for Related Content PubMed PubMed Citation Articles by Kan, L.-s. Articles by Huang, D.-H.

The Paperclip Triplex: Understanding the Role of Apex Residues in Tight Turns

Lou-sing Kan ^*, Laura Pasternack , Ming-Tsair Wey ^*, Yu-Yu Tseng ^* and Dee-Hua Huang 

^* Institute of Chemistry, Academia Sinica, Taipei, Taiwan 11529; and The Scripps Research Institute, La Jolla, California 92037 USA

Correspondence: Address reprint requests to Lou-sing Kan, E-mail: lskan{at}chem.sinica.edu.tw.

In this study, we investigate the role of the apex nucleotides of the two turns found in the intramolecular "paperclip" type triplex DNA formed by 5'-TCTCTCCTCTCTAGAGAG-3'. Our previously published structure calculations show that residues C₇-A₁₈ form a hairpin turn via Watson-Crick basepairing and residues T₁-C₆ bind into the major groove of the hairpin via Hoogsteen basepairing resulting in a broad turn of the T₁-T₁₂ 5'-pyrimidine section of the DNA. We find that only the C₆C₇/G₁₈ apex triad (and not the T₁₂A₁₃/T₁ apex triad) is required for intramolecular triplex formation, is base independent, and occurs whether the purine section is located at the 5' or 3' end of the sequence. NMR spectroscopy and molecular dynamics simulations are used to investigate a bimolecular complex (which retains only the C₆C₇/G₁₈ apex) in which a pyrimidine strand 5'- TCTCTCCTCTCT-3' makes a broad fold stabilized by the purine strand 5'-AGAGAG-3' via Watson Crick pairing to the T₈-T₁₂ and Hoogsteen basepairing to T₁-T₅ of the pyrimidine strand. Interestingly, this investigation shows that this 5'-AGAGAG-3' oligo acts as a new kind of triplex forming oligonucleotide, and adds to the growing number of triplex forming oligonucleotides that may prove useful as therapeutic agents.

This article has been cited by other articles:

				M. Duca, P. Vekhoff, K. Oussedik, L. Halby, and P. B. Arimondo The triple helix: 50 years later, the outcome Nucleic Acids Res., September 1, 2008; 36(16): 5123 - 5138. [Abstract] [Full Text] [PDF]