PMID: 9185577Jul 1, 1997Paper

Formation of a G-tetrad and higher order structures correlates with biological activity of the RelA (NF-kappaB p65) 'antisense' oligodeoxynucleotide

Nucleic Acids Research
L BenimetskayaC A Stein

Abstract

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 acti...Continue Reading

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Citations

May 21, 1998·Antisense & Nucleic Acid Drug Development·C A Stein
Aug 27, 1999·Antisense & Nucleic Acid Drug Development·S SeidmanH Soreq
Jul 25, 2000·Antisense & Nucleic Acid Drug Development·R M HudziakP L Iversen
Apr 12, 2003·Nucleic Acids Research·Virna DapićPaula J Bates
Jan 1, 2013·Nucleic Acids Research·Brighton SamatangaFrédéric H-T Allain
Nov 24, 2007·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·I V Lebedeva, C A Stein
Apr 2, 2003·Expert Opinion on Therapeutic Targets·Robert G RamsayThomas J Gonda
Mar 8, 2011·International Immunopharmacology·Robert F AshmanPetar S Lenert
May 21, 2009·Experimental and Molecular Pathology·Paula J BatesJohn O Trent
Nov 3, 2004·Toxicology and Applied Pharmacology·Tracey L H JasonRandal W Berg
Aug 31, 2002·Analytical Biochemistry·Paula J BatesDonald M Miller
Jan 5, 2010·Methods : a Companion to Methods in Enzymology·Alissa M HulstrandDouglas W Houston
Sep 7, 2001·The Journal of Clinical Investigation·C A Stein
Mar 17, 2006·Antiviral Research·Paul F TorrenceJohn D Morrey
Mar 30, 1999·Nature Biotechnology·C A Stein
Jun 9, 2004·The Journal of Biological Chemistry·Christina C N WuDennis A Carson
Sep 3, 1999·The Journal of Biological Chemistry·P J BatesD M Miller
Apr 16, 2019·Frontiers in Pharmacology·Davide Di FuscoGiovanni Monteleone

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