Helm M, Kopka M L, Sharma S K, Lown J W, Giegé R
Département 'Mécanismes et Macromolécules de la Synthèse Protéique et Cristallogenèse', UPR 9002, Institut de Biologie Moléculaire et Cellulaire du CNRS, 15 rue René Descartes, Strasbourg Cedex, F 67084, France.
Biochem Biophys Res Commun. 2001 Mar;281(5):1283-90. doi: 10.1006/bbrc.2001.4503.
Imidazole and compounds containing imidazole residues have been shown to cleave RNA in an RNase A-mimicking manner. Di-imidazole lexitropsin is a compound which is derived from the polyamide drugs distamycin and netropsin essentially by the replacement of two pyrrole heterocycles with N-methyl-imidazole residues. This enables it to bind to the minor groove of B-DNA in a sequence-specific manner. We demonstrate here that this lexitropsin derivative has RNA cleavage activity, as tested on model RNAs. Optimal cleavage conditions and cleavage specificity resemble those known from other imidazole conjugates and are thus consistent with an RNase A type cleavage mechanism. The optimum concentration of the compound for cleavage is similar to previously investigated imidazole-based RNase mimics. As a whole new class of chemical compounds capable of interacting with nucleic acids through extensive hydrogen bonding, these imidazole containing compounds constitute promising scaffolds and ligands, for the construction of novel RNase mimics with high affinity.
咪唑及含有咪唑残基的化合物已被证明能以模仿核糖核酸酶A的方式切割RNA。双咪唑偏嗜菌素是一种化合物，它基本上是由聚酰胺药物偏端霉素和纺锤菌素衍生而来，即将两个吡咯杂环替换为N-甲基咪唑残基。这使得它能够以序列特异性的方式与B-DNA的小沟结合。我们在此证明，这种偏嗜菌素衍生物具有RNA切割活性，这是在模型RNA上测试得出的。最佳切割条件和切割特异性与其他咪唑缀合物已知的情况相似，因此与核糖核酸酶A类型的切割机制一致。该化合物切割的最佳浓度与先前研究的基于咪唑的核糖核酸酶模拟物相似。作为一类全新的能够通过广泛氢键与核酸相互作用的化合物，这些含咪唑化合物构成了用于构建具有高亲和力的新型核糖核酸酶模拟物的有前景的支架和配体。
