Nucleic Acids Research, Vol 25, Issue 13 2648-2656, Copyright © 1997 by Oxford University Press
L Benimetskaya, M Berton, A Kolbanovsky, S Benimetsky and CA Stein
We have examined the behavior of the phosphorothioate antisense Rel A
(NF-kappaB p65) oligodeoxynucleotide (oligo) and related molecules. Because
of the presence of a G-tetrad near its 5'terminus, this molecule is capable
of forming tetraplexes and other higher order structures in a temperature
and time dependent manner. The G-tetrad in the phosphodiester congener is
protected from methylation by dimethylsulfate when the oligomer is
3'-phosphorylated. However, this protection is completely lost when it is
5'phosphorylated, indicating that the formation of at least some higher
order structures has been blocked. In addition, we also prevented tetraplex
formation by substitution of 7-deazaguanosine (7-DG) for guanosine at
several positions within and outside of the tetrad. This substitution
retains Watson-Crick base pair hybridization but prevents Hoogsteen
base-pair interactions. When murine K-Balb cells were treated with 20microM
antisense RelA oligo, complete blockade of nuclear translocation of RelA
was observed. However, this effect was virtually entirely abrogated in most
cases by 7-DG substitution within the tetrad, but retained when the
substitution was made 3' to the tetrad. The AS RelA- induced downregulation
of Sp-1 activity behaved similarly after 7-DG substitution. Thus, the
parent phosphorothioate AS RelA molecule cannot be a Watson-Crick antisense
agent. However, these conclusions cannot be extrapolated to other G-tetrad
containing oligomers and each must be evaluated individually.
ARTICLES
Formation of a G-tetrad and higher order structures correlates with biological activity of the RelA (NF-kappaB p65) 'antisense' oligodeoxynucleotide
Department of Medicine, Columbia University, College of Physicians and Surgeons, 630 West 168 Street, New York, NY 10032, USA.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. C. Girvan, Y. Teng, L. K. Casson, S. D. Thomas, S. Juliger, M. W. Ball, J. B. Klein, W. M. Pierce Jr., S. S. Barve, and P. J. Bates AGRO100 inhibits activation of nuclear factor-{kappa}B (NF-{kappa}B) by forming a complex with NF-{kappa}B essential modulator (NEMO) and nucleolin. Mol. Cancer Ther., July 1, 2006; 5(7): 1790 - 1799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Napoli, U. Negri, F. Arcamone, M. L. Capobianco, G. M. Carbone, and C. V. Catapano Growth inhibition and apoptosis induced by daunomycin-conjugated triplex-forming oligonucleotides targeting the c-myc gene in prostate cancer cells Nucleic Acids Res., January 30, 2006; 34(2): 734 - 744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Kerkmann, L. T. Costa, C. Richter, S. Rothenfusser, J. Battiany, V. Hornung, J. Johnson, S. Englert, T. Ketterer, W. Heckl, et al. Spontaneous Formation of Nucleic Acid-based Nanoparticles Is Responsible for High Interferon-{alpha} Induction by CpG-A in Plasmacytoid Dendritic Cells J. Biol. Chem., March 4, 2005; 280(9): 8086 - 8093. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Carbone, S. Napoli, A. Valentini, F. Cavalli, D. K. Watson, and C. V. Catapano Triplex DNA-mediated downregulation of Ets2 expression results in growth inhibition and apoptosis in human prostate cancer cells Nucleic Acids Res., August 16, 2004; 32(14): 4358 - 4367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. C. N. Wu, J. Lee, E. Raz, M. Corr, and D. A. Carson Necessity of Oligonucleotide Aggregation for Toll-like Receptor 9 Activation J. Biol. Chem., August 6, 2004; 279(32): 33071 - 33078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Dapic, V. Abdomerovic, R. Marrington, J. Peberdy, A. Rodger, J. O. Trent, and P. J. Bates Biophysical and biological properties of quadruplex oligodeoxyribonucleotides Nucleic Acids Res., April 15, 2003; 31(8): 2097 - 2107. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. M. Carbone, E. M. McGuffie, A. Collier, and C. V. Catapano Selective inhibition of transcription of the Ets2 gene in prostate cancer cells by a triplex-forming oligonucleotide Nucleic Acids Res., February 1, 2003; 31(3): 833 - 843. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Benimetskaya, P. Miller, S. Benimetsky, A. Maciaszek, P. Guga, S. L. Beaucage, A. Wilk, A. Grajkowski, A. L. Halperin, and C. A. Stein Inhibition of Potentially Anti-Apoptotic Proteins by Antisense Protein Kinase C-alpha (Isis 3521) and Antisense bcl-2 (G3139) Phosphorothioate Oligodeoxynucleotides: Relationship to the Decreased Viability of T24 Bladder and PC3 Prostate Cancer Cells Mol. Pharmacol., December 1, 2001; 60(6): 1296 - 1307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Xu, F. Hamhouyia, S. D. Thomas, T. J. Burke, A. C. Girvan, W. G. McGregor, J. O. Trent, D. M. Miller, and P. J. Bates Inhibition of DNA Replication and Induction of S Phase Cell Cycle Arrest by G-rich Oligonucleotides J. Biol. Chem., November 9, 2001; 276(46): 43221 - 43230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. d. Diesbach, C. Berens, F. N'Kuli, M. Monsigny, E. Sonveaux, R. Wattiez, and P. J. Courtoy Identification, purification and partial characterisation of an oligonucleotide receptor in membranes of HepG2 cells Nucleic Acids Res., February 15, 2000; 28(4): 868 - 874. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Prasad, S. Hashim, A. Mukhopadhyay, S. K. Basu, and R. P. Roy Oligonucleotides Tethered to a Short Polyguanylic Acid Stretch Are Targeted to Macrophages: Enhanced Antiviral Activity of a Vesicular Stomatitis Virus-Specific Antisense Oligonucleotide Antimicrob. Agents Chemother., November 1, 1999; 43(11): 2689 - 2696. [Abstract] [Full Text]
|
|
|
|
|
|
P. J. Bates, J. B. Kahlon, S. D. Thomas, J. O. Trent, and D. M. Miller Antiproliferative Activity of G-rich Oligonucleotides Correlates with Protein Binding J. Biol. Chem., September 10, 1999; 274(37): 26369 - 26377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Gewirtz, D. L. Sokol, and M. Z. Ratajczak Nucleic Acid Therapeutics: State of the Art and Future Prospects Blood, August 1, 1998; 92(3): 712 - 736. [Full Text] [PDF]
|
|