Laboratories of Medicinal Chemistry, Clemson University, Clemson, South Carolina 29634, USA.
Biochemistry. 2010 Jan 26;49(3):452-69. doi: 10.1021/bi9016796.
Recent developments have indicated that aminoglycoside binding is not limited to RNA, but to nucleic acids that, like RNA, adopt conformations similar to its A-form. We further sought to expand the utility of aminoglycoside binding to B-DNA structures by conjugating neomycin, an aminoglycoside antibiotic, with the B-DNA minor groove binding ligand Hoechst 33258. Envisioning a dual groove binding mode, we have extended the potential recognition process to include a third, intercalative moiety. Similar conjugates, which vary in the number of binding moieties but maintain identical linkages to allow direct comparisons to be made, have also been prepared. We report herein novel neomycin- and Hoechst 33258-based conjugates developed in our laboratories for exploring the recognition potential with B-DNA. Spectroscopic studies such as UV melting, differential scanning calorimetry, isothermal fluorescence titrations, and circular dichroism together illustrate the triple recognition of the novel conjugate containing neomycin, Hoechst 33258, and pyrene. This study represents the first example of DNA molecular recognition capable of minor versus major groove recognition in conjunction with intercalation.
最近的研究进展表明，氨基糖苷类的结合并不仅限于 RNA，还包括与 RNA 类似，能采取 A 型构象的核酸。我们进一步寻求通过将氨基糖苷类抗生素新霉素与 B-DNA 小沟结合配体 Hoechst 33258 缀合，来扩展氨基糖苷类结合到 B-DNA 结构的应用。设想出一种双重沟结合模式，我们已经将潜在的识别过程扩展到包括第三个嵌入部分。我们还制备了类似的缀合物，它们在结合部分的数量上有所不同，但保持相同的连接，以便可以进行直接比较。我们在此报告了我们实验室开发的新型新霉素和 Hoechst 33258 缀合物，用于探索与 B-DNA 的识别潜力。紫外熔融、差示扫描量热法、等温荧光滴定和圆二色性等光谱研究共同说明了新型缀合物中包含的新霉素、Hoechst 33258 和芘的三重识别。这项研究代表了第一个能够与嵌入相结合的小沟与大沟识别的 DNA 分子识别的例子。
