In a matched pair of oligonucleotides (ODNS) each member of the pair is complementary or substantially complementary in the Watson Crick sense to a target sequence of duplex nucleic acid where the two strands of the target sequence are themselves complementary to one another. The ODNs include modified bases of such nature that the modified base forms a stable hydrogen bonded base pair with the natural partner base, but does not form a stable hydrogen bonded base pair with its modified partner. This is accomplished when in a hybridized structure the modified base is capable of forming two or more hydrogen bonds with its natural complementary base, but only one hydrogen bond with its modified partner. Due to the lack of stable hydrogen bonding with each other, the matched pair of oligonucleotides have a melting temperature under physiological or substantially physiological conditions of approximately 40.degree. C. or less. However each of the matched ODN pair of the invention forms a substantially stable hybrid with the target sequence in each strand of the duplex nucleic acid. The hybrids of target duplex nucleic acids formed with the ODN pairs of the invention are useful for gene mapping and in diagnostic and therapeutic applications.
在一对配对的寡核苷酸(ODNS)中,每个成员的配对成员在沃森-克里克意义上与双链核酸的目标序列互补或基本互补,其中目标序列的两条链本身是互补的。ODNS包括具有这种性质的修饰碱基,即修饰碱基与天然配对碱基形成稳定的氢键配对,但与其修饰配对碱基不形成稳定的氢键配对。当在杂交结构中,修饰碱基能够与其天然互补碱基形成两个或更多氢键,但只能与其修饰配对碱基形成一个氢键时,就实现了这一点。由于彼此之间缺乏稳定的氢键结合,配对的寡核苷酸在生理条件或基本生理条件下的熔化温度约为40摄氏度或更低。然而,本发明的每一对匹配的ODN对都与双链核酸的每条链中的目标序列形成基本稳定的杂交。使用本发明的ODN对形成的目标双链核酸的杂交对于
基因定位以及诊断和治疗应用是有用的。