       Document 0316
 DOCN  M9630316
 TI    Single strand targeted triplex formation: targeting purine-pyrimidine
       mixed sequences using abasic linkers.
 DT    9603
 AU    Kandimalla ER; Manning AN; Venkataraman G; Sasisekharan V; Agrawal S;
       Hybridon, Inc., Worcester, MA 01605, USA.
 SO    Nucleic Acids Res. 1995 Nov 11;23(21):4510-7. Unique Identifier :
       AIDSLINE MED/96091203
 AB    Foldback triplex-forming oligonucleotides (FTFOs) that contain an abasic
       linker, [2-(4-aminobutyr-1-yl)-1,3-propanediol] (APD linker), in the
       Hoogsteen domain against pyrimidine bases of a C:G and a T:A base pair
       were studied for their relative stability and sequence specificity of
       triplex formation. In general, the APD linker has less destabilizing
       effect against a C:G base pair than a T:A base pair. Incorporation of
       three APD linker moieties resulted in decreased binding to the target,
       which was comparable to results observed with three imperfectly matched
       natural base triplets. The APD linker incorporation did not result in
       the loss of sequence specificity of FTFOs, unlike in the case of normal
       triplex-forming oligonucleotides (TFOs). The introduction of a
       positively charged abasic linker, however, resulted in decreased
       stability of the triplex, because of loss of hydrogen bonding and
       stacking interactions in the major groove. The results of a molecular
       modeling study show that APD linker can be readily incorporated without
       any change in the conformation of the natural sugar-phosphate backbone
       conserving overall triple helix geometry. Further, the modeling study
       suggests a hydrogen bond formation between the amino group of linker and
       N4 of cytosine mediated by a solvent molecule (water) in the floor of
       the base triplet in addition to a contribution from the positive charge
       on the APD linker amino group. Either a direct or water-mediated
       hydrogen bond between the amino group of the APD linker and the O4 of
       thymine is unlikely when the linker is placed against a T:A base pair.
 DE    Base Composition  Base Sequence  Butylamines/CHEMISTRY  Comparative
       Study  Computer Simulation  *Genes, gag  HIV-1/*GENETICS  Models,
       Molecular  Molecular Sequence Data  *Nucleic Acid Conformation  Nucleic
       Acid Denaturation  Nucleic Acid Hybridization
       Oligodeoxyribonucleotides/*CHEMISTRY  Propanediols/CHEMISTRY  RNA,
       Messenger/CHEMISTRY  RNA, Viral/*CHEMISTRY  Spectrophotometry,
       Ultraviolet  Structure-Activity Relationship  JOURNAL ARTICLE

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

