title: Oligonucleotides containing 2-aminoadenine and 2-thiothymine act as selectively binding complementary agents.
abstract: A pair of complementary oligodeoxynucleotides (ODNs) uniformly substituted with 2-amino-adenine (A') in place of adenine and 2-thiothymine (T') in place of thymine did not hybridize to each other but did form very stable hybrids with unmodified complementary ODNs. These unusual properties were a consequence of the hydrogen-bonding properties of the two base analogs. Thermal denaturation studies of short duplexes which contained these bases demonstrated that the A'-T and A-T' doublets formed stable base pairs whereas the A'-T' doublet acted like a mismatch. Complementary ODNs substituted with these base analogs are referred to as SBC or selectively binding complementary ODNs. When used as a pair, these single-stranded ODNs invaded the ends of homologous duplexes and formed stable three-arm junctions under conditions where unmodified ODNs failed to give a product. SBC ODNs have a fundamental thermodynamic advantage in hybridizing to short segments of double-stranded nucleic acid and represent a new approach for the design of oligomeric probes and antisense agents. Many secondary structure features present in long single-stranded nucleic acids should be accessible to these reagents.
authors.affiliation: Epoch Pharmaceuticals, Inc., Bothell, Washington 98021, USA.
authors.forename: I V
authors.initials: IV
authors.lastname: Kutyavin
authors.forename: R L
authors.initials: RL
authors.lastname: Rhinehart
authors.forename: E A
authors.initials: EA
authors.lastname: Lukhtanov
authors.forename: V V
authors.initials: VV
authors.lastname: Gorn
authors.forename: R B
authors.initials: RB
authors.lastname: Meyer
authors.forename: H B
authors.initials: HB
authors.lastname: Gamper
mesh_terms: D015075:2-Aminopurine / Q000031:analogs & derivatives* / Q000378:metabolism; D001483:Base Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D006860:Hydrogen Bonding; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides / Q000378:metabolism*; D013816:Thermodynamics; D013941:Thymine / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D009838:Oligodeoxyribonucleotides; D015075:2-Aminopurine; C007300:2,6-diaminopurine; C101233:2-thiothymine; D013941:Thymine