Document 0791
 DOCN  M94B0791
 TI    Hyperstabilization of sense-antisense duplexes and inhibition of
       translation (Meeting abstract).
 DT    9412
 AU    Kim DY; Shih DS; Cho DY; Swenson DH; School of Veterinary Medicine,
       Louisiana State University, Baton; Rouge, LA 70803
 SO    Proc Annu Meet Am Assoc Cancer Res; 35:A1835 1994. Unique Identifier :
       AIDSLINE ICDB/94603521
 AB    The antitumor agents CC-1065 and U-71,184 raise the Tm of
       double-stranded DNA. We undertook this study to determine if these
       agents could hyperstabilize RNA-DNA (sense-antisense) duplexes or DNA
       duplexes in which one strand contained phosphorothioate (PS) or
       methylphosphonate (MP) internucleotide linkages. Sequences 1 and 2
       (5'-TTACTTCAGTTATCAGACCA-3'; CC-1065 target underlined) were from the
       env gene of equine infectious anemia virus (EIAV). Seq 1 was DNA and seq
       2 was RNA. Antisense seq 3, 4 and 5 were complementary to seqs 1 and 2
       and were comprised of phosphodiester (PO), PS and MP, resp. Duplexes
       from seq1-seq3, seq1-seq4, seq1-seq5 all bound CC-1065 and showed
       elevations in Tm of 17 to 21 C. Poly(rA)-oligo(dT20) and
       oligo(dA20)-oligo(dT20) showed increases in Tm of 28 and 31 C, resp,
       when bound to CC-1065. Seq2-seq3 and seq2-seq4 each bound 1
       CC-1065/duplex, but insufficient material was available to evaluate Tm.
       U-71,184 caused strong elevation of Tm (greater than 15 C) only with
       seq1-seq5 and oligo(dA20)-oligo(dT20). An mRNA transcript (585-mer) of
       EIAV was targeted approx 200 bases downstream from the initiation site
       with a 20-mer PO antisense oligonucleotide. Translation (wheat germ
       extract) was inhibited in a dose-dependent fashion at antisense:mRNA
       ratios ranging from 10 to 72, and concomitant incubations of the
       duplexes with CC-1065 (4x compared to antisense) caused significant
       enhanced depression of translation for the higher doses. A 20-mer sense
       sequence, incubated with the MRNA, with and without CC-1065, had little
       or no effect on translation. Antisense oligonucleotides tethered to
       CC-1065-like ligands may yield duplexes with MRNA of high stability.
 DE    Base Sequence  *Genes, env  Infectious Anemia Virus, Equine/*GENETICS
       Molecular Sequence Data  Oligodeoxyribonucleotides/*TOXICITY
       Oligonucleotides, Antisense/*TOXICITY  RNA, Messenger/BIOSYNTHESIS
       Transcription, Genetic  Translation, Genetic/*DRUG EFFECTS
       Wheat/METABOLISM  MEETING ABSTRACT

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