       Document 0215
 DOCN  M9610215
 TI    Design, biochemical, biophysical and biological properties of
       cooperative antisense oligonucleotides.
 DT    9601
 AU    Kandimalla ER; Manning A; Lathan C; Byrn RA; Agrawal S; Hybridon, Inc.,
       Worcester, MA 01604, USA.
 SO    Nucleic Acids Res. 1995 Sep 11;23(17):3578-84. Unique Identifier :
       AIDSLINE MED/96032854
 AB    Short oligonucleotides that can bind to adjacent sites on target mRNA
       sequences are designed and evaluated for their binding affinity and
       biological activity. Sequence-specific binding of short tandem
       oligonucleotides is compared with a full-length single oligonucleotide
       (21mer) that binds to the same target sequence. Two short
       oligonucleotides that bind without a base separation between their
       binding sites on the target bind cooperatively, while oligonucleotides
       that have a one or two base separation between the binding
       oligonucleotides do not. The binding affinity of the tandem
       oligonucleotides is improved by extending the ends of the two
       oligonucleotides with complementary sequences. These extended sequences
       form a duplex stem when both oligonucleotides bind to the target,
       resulting in a stable ternary complex. RNase H studies reveal that the
       cooperative oligonucleotides bind to the target RNA with sequence
       specificity. A short oligonucleotide (9mer) with one or two mismatches
       does not bind at the intended site, while longer oligonucleotides
       (21mers) with one or two mismatches still bind to the same site, as does
       a perfectly matched 21mer, and evoke RNase H activity. HIV-1 inhibition
       studies reveal an increase in activity of the cooperative
       oligonucleotide combinations as the length of the dimerization domain
       increases.
 DE    Antiviral Agents/*CHEMISTRY/PHARMACOLOGY  Base Sequence  Heat
       HIV-1/*GENETICS  Molecular Sequence Data  Nucleic Acid Denaturation
       Nucleic Acid Hybridization  Oligonucleotides,
       Antisense/*CHEMISTRY/PHARMACOLOGY  Ribonuclease H, Calf
       Thymus/METABOLISM  RNA, Viral/CHEMISTRY  Structure-Activity Relationship
       Virus Replication/DRUG EFFECTS  JOURNAL ARTICLE

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

