       Document 0053
 DOCN  M9580053
 TI    Single strand targeted triplex-formation. Destabilization of guanine
       quadruplex structures by foldback triplex-forming oligonucleotides.
 DT    9506
 AU    Kandimalla ER; Agrawal S; Hybridon, Inc., Worcester, MA 01605, USA.
 SO    Nucleic Acids Res. 1995 Mar 25;23(6):1068-74. Unique Identifier :
       AIDSLINE MED/95249361
 AB    Oligonucleotides that can hybridize to single-stranded complementary
       polypurine nucleic acid targets by Watson-Crick base pairing as well as
       by Hoogsteen base pairing, referred to here as foldback triplex-forming
       oligonucleotides (FTFOs), have been designed. These oligonucleotides
       hybridize with target nucleic acid sequences with greater affinity than
       antisense oligonucleotides, which hybridize to the target sequence only
       by Watson-Crick hydrogen bonding [Kandimalla, E. R. and Agrawal, S.
       Gene(1994) 149, 115-121 and references cited therein]. FTFOs have been
       studied for their ability to destabilize quadruplexes formation by RNA
       or DNA target sequences. The influence of various DNA/RNA compositions
       of FTFOs on their ability to destabilize RNA and DNA quadruplexes has
       been examined. The ability of the FTFOs to destabilize quadruplex
       structures is related to the structurally and thermodynamically stable
       foldback triplex formed between the FTFO and its target sequence.
       Antisense oligonucleotides (DNA or RNA) that can form only a
       Watson-Crick double helix with the target sequence are unable to
       destabilize quadruplex structures of RNA and DNA target sequences and
       are therefore limited in their repertoire of target sequences. The
       quadruplex destabilization ability of FTFOs is dependent on the nature
       of the cation present in solution. The RNA quadruplex destabilization
       ability of FTFOs is -20% higher in the presence of sodium ion than
       potassium ion. The use of FTFOs, which can destabilize quadruplex
       structure, opens up new areas for development of oligonucleotide-based
       therapeutics, specifically, targeting guanine-rich sequences that exist
       at the ends of pro- and eukaryotic chromosomes and dimerization regions
       of retroviral RNA.
 DE    Base Sequence  DNA/*CHEMISTRY  DNA, Antisense/CHEMISTRY  Genes,
       gag/GENETICS  Guanine/PHYSIOLOGY  Hydrogen-Ion Concentration
       HIV-1/GENETICS  Methylation  Molecular Sequence Data  *Nucleic Acid
       Conformation  Oligodeoxyribonucleotides/*CHEMISTRY/CHEMICAL
       SYNTHESIS/ISOLATION  & PURIF  Potassium/CHEMISTRY  RNA/*CHEMISTRY  RNA,
       Antisense/CHEMISTRY  Sodium/CHEMISTRY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

