Nelson J S, Giver L, Ellington A D, Letsinger R L
Department of Chemistry, Northwestern University, Evanston, Illinois 60208, USA.
Biochemistry. 1996 Apr 23;35(16):5339-44. doi: 10.1021/bi952917u.
A bridge containing a rigid trans-stilbene group, -P(O)(O-)O(CH2)3NHC(O)- C6H4-CH=CHC6H4C(O)NH(CH2)3OP(O)(O-)-, has been incorporated into several oligonucleotide sequences based on the minimal Rev Binding Element (RBE) of HIV-1. This bridge was found to be effective as a UUCG tetraloop in stabilizing short RNA duplex structures containing mismatched bases and bulged out nucleotide residues and to be more effective than either a TTTT loop or a triethyleneglycol linker in stabilizing similar DNA structures. Evaluation of stilbene-containing RNA RBE sequences of varying length for their ability to bind the Rev protein of HIV-1 showed that a 22-nucleotide stilbenedicarboxamide conjugate bound Rev almost as well as a 94-base fragment of the Rev Responsive Element (RRE). A DNA hairpin mimetic with the same sequence was incapable of Rev binding. Taken together, these experiments serve as an example for how in vitro selection and chemical modification can be combined to generate high-affinity mimetics of nucleic acid sequence and structure.
一种含有刚性反式芪基团-P(O)(O-)O(CH2)3NHC(O)-C6H4-CH=CHC6H4C(O)NH(CH2)3OP(O)(O-)-的桥连结构已被引入基于HIV-1最小Rev结合元件（RBE）的多个寡核苷酸序列中。发现该桥连结构作为一个UUCG四环在稳定含有错配碱基和突出核苷酸残基的短RNA双链体结构方面是有效的，并且在稳定类似的DNA结构方面比TTTT环或三乙二醇连接子更有效。对不同长度的含芪RNA RBE序列结合HIV-1 Rev蛋白能力的评估表明，一个22个核苷酸的芪二甲酰胺缀合物结合Rev的能力几乎与Rev反应元件（RRE）的一个94个碱基的片段相同。具有相同序列的DNA发夹模拟物则无法结合Rev。综上所述，这些实验为例说明了如何将体外筛选和化学修饰相结合以生成核酸序列和结构的高亲和力模拟物。
