Sequence and structural selectivity of nucleic acid binding ligands
Sequence and structural selectivity of nucleic acid binding ligands
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DOI：
10.1021/bi992070s
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发表时间：
1999-12-07
期刊：
影响因子：
2.9
通讯作者：
Chaires, JB
中科院分区：
文献类型：
--
作者：
Ren, JS;Chaires, JB
15种不同的DNA结合剂的序列和结构的选择性进行了探讨，使用一种新的，严格的，竞争透析程序。在竞争透析方法中，针对共同的配体溶液透析13种不同的核酸结构。更多的配体积累在透析管中，含有具有最高配体结合亲和力的结构形式。试验中包括的DNA结构形式范围从单链形式，通过各种双链体形式，到多链三链体和四链体形式。左手的Z-DNA，RNA和DNA-RNA杂交也被代表。标准嵌入剂（乙锭，柔红霉素，放线菌素D）作为对照化合物，并发现其结构结合的偏好完全符合他们以前发表的行为。标准沟结合剂（DAPI、dystamycin和netropsin）显示出对富含AT的双链体DNA形式的强烈偏好，沿着与聚（da）-[聚（dT）]（2）三聚体的明显强结合。热变性研究表明，明显的三倍体结合是复杂的，并可能导致从第三链的位移。推定的三倍体（BePI、coralyne和小檗碱）和四倍体[H2 TmPyP、5，10，15，20-四[4-（三甲基铵基）苯基]-21H，23H-卟啉和N-甲基中卟啉IX]选择性试剂在许多情况下显示出比从公开的报告中预期的更少的显著结合选择性，所述公开的报告将它们的结合仅与少数结构形式进行比较。Coralyne被发现强烈结合到单链聚（dA），一种新的和以前未报道的相互作用。最后，三种化合物（Berenil，色霉素A，和pyrenemethylamine），其结构的偏好在很大程度上是未知的进行了检查。芘乙胺表现出一个意想不到的和前所未有的双链聚（dAdT）的偏好。
The sequence and structural selectivity of 15 different DNA binding agents was explored using a novel, thermodynamically rigorous, competition dialysis procedure. In the competition dialysis method, 13 different nucleic acid structures were dialyzed against a common ligand solution. More ligand accumulated in the dialysis tube containing the structural form with the highest ligand binding affinity. DNA structural forms included in the assay ranged from single-stranded forms, through a variety of duplex forms, to multistranded tripler and tetraplex forms. Left-handed Z-DNA, RNA, and a DNA-RNA hybrid were also represented. Standard intercalators (ethidium, daunorubicin, and actinomycin D) served as control compounds and were found to show structural binding preferences fully consistent with their previously published behavior. Standard groove binding agents (DAPI,dystamycin, and netropsin) showed a strong preference for AT-rich duplex DNA forms, along with apparently strong binding to the poly(da)-[poly(dT)](2) tripler. Thermal denaturation studies revealed the apparent tripler binding to be complex, and perhaps to result from displacement of the third strand. Putative tripler (BePI, coralyne, and berberine) and tetraplex [H2TmPyP, 5,10,15,20-tetrakis [4-(trimethylammonio)phenyl] -21H,23H-porphine, and N-methyl mesoporphyrin IX] selective agents showed in many cases less dramatic binding selectivity than anticipated from published reports that compared their binding to only a few structural forms. Coralyne was found to bind strongly to single-stranded poly(dA), a novel and previously unreported interaction. Finally, three compounds (berenil, chromomycin A, and pyrenemethylamine) whose structural preferences are largely unknown were examined. Pyrenemethylamine exhibited an unexpected and unprecedented preference for duplex poly(dAdT).