title: Hybrid oligonucleotides: synthesis, biophysical properties, stability studies, and biological activity.
abstract: We have designed and synthesized hybrid oligonucleotides 2-5, as analogues of oligodeoxynucleoside phosphorothioates, in an effort to have agents with improved 'antisense activity' with reduced phosphorothioate content. The hybrid oligonucleotides contain segments of 2'-O-methyl ribonucleoside phosphoric diesters and oligodeoxynucleoside phosphorothioates. Thus, compared with the 'all' phosphorothioate analogues 1 and 6, the analogues 2-5 showed significantly reduced effect on complement activation. In addition, thermal denaturation studies with complementary RNA revealed that the analogues 2-5 had higher Tm compared with that with oligodeoxynucleoside phosphorothioates. Additionally, the RNA component of the oligo/ RNA duplex is efficiently cleaved by RNase H, the site of endonucleolytic cleavage being dictated by the length of the oligodeoxynucleoside phosphorothioate segment.
authors.affiliation: Hybridon Inc., Worcester, MA 01605, USA.
authors.forename: D
authors.initials: D
authors.lastname: Yu
authors.forename: R P
authors.initials: RP
authors.lastname: Iyer
authors.forename: D R
authors.initials: DR
authors.lastname: Shaw
authors.forename: J
authors.initials: J
authors.lastname: Lisziewicz
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: Z
authors.initials: Z
authors.lastname: Jiang
authors.forename: A
authors.initials: A
authors.lastname: Roskey
authors.forename: S
authors.initials: S
authors.lastname: Agrawal
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry*; D015941:Complement Hemolytic Activity Assay; D006358:Hot Temperature; D009691:Nucleic Acid Denaturation; D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry*; D016914:Ribonuclease H / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D009841:Oligonucleotides; D016914:Ribonuclease H