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Recognition of B-DNA by neomycin-Hoechst 33258 conjugates

机译:Neomycin-Hoechst 33258缀合物对B-DNA的识别

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Recent developments have indicated that aminoglycoside binding is limited not to RNA but to nucleic acids that, like RNA, adopt conformations similar to the A-form. We have 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. Described herein are novel neomycin-Hoechst 33258 conjugates developed for exploring B-DNA groove recognition. We have varied the two reported conjugates in linker length and composition in an effort to improve our understanding of the spatial differences that define B-DNA binding. Spectroscopic studies such as ultraviolet (UV) melting, isothermal fluorescence titrations, differential scanning calorimetry (DSC), and circular dichroism (CD) together illustrate the mode of binding by such conjugates. Both conjugates exhibit enhanced thermal stabilization of A, T rich duplexes when compared to Hoechst 33258.
机译:最近的发展已经表明,氨基糖苷脂结合仅限于RNA,而是对核酸,如RNA,采用与A形类似的构象。 我们进一步通过缀合新霉素,氨基糖苷抗生素与B-DNA轻微沟结合配体Hoechst 33258扩展了氨基糖苷结合与B-DNA结构的效用。本文描述了新的新霉素-Hoechst 33258缀合物,用于探索B- DNA Groove识别。 我们在接头长度和组合物中改变了两个报告的共轭,以提高我们对定义B-DNA结合的空间差异的理解。 诸如紫外(UV)熔化,等温荧光滴定,差分扫描量热法(DSC)的光谱研究以及圆形二色性(CD)一起说明了这种缀合物的结合方式。 与Hoechst 33258相比,缀合物的热稳定性增强了A,T丰富的双工。

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