Subtle recognition of 14-base pair DNA sequences via threading polyintercalation.
Subtle recognition of 14-base pair DNA sequences via threading polyintercalation.
复制标题
通过螺纹多分辨率对14碱基对DNA序列的微妙识别。
DOI：
10.1021/bi300317n
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发表时间：
2012-06-05
期刊：
影响因子：
2.9
通讯作者：
Iverson BL
中科院分区：
文献类型：
--
作者：
Smith AR;Ikkanda BA;Holman GG;Iverson BL
以序列特异性方式结合DNA的小分子可以作为抗生素、抗病毒药物或抗癌药物，因为它们具有操纵基因表达的潜在能力。我们的实验室开发了基于1,4,5,8-萘二亚胺（NDI）单元的穿线多插层器，通过灵活的肽连接器以头到尾的方式连接。先前，一个由交替的小-大-小凹槽结合模块组成的线程式四极器被证明可以特异性地结合一个14 bp的DNA序列，其解离半衰期为16天[Holman， g.g.等（2011）Nat. Chem. 3,875 - 881]。本文描述了一种新的基于ndi的四轴加速器，它具有不同的主凹槽结合模块和一个小凹槽结合模块的反向N到C方向。DNA酶I足迹分析和动力学分析表明，这些新的四分子加速器能够分辨出相差1或2 bp的14 bp的DNA结合位点，最多可达30倍。发现相对亲和力与解离率密切相关，而dna结合分子的整体C2对称性似乎有助于提高关联率。
Small molecules that bind DNA in a sequence-specific manner could act as antibiotic, antiviral, or anticancer agents because of their potential ability to manipulate gene expression. Our laboratory has developed threading polyintercalators based on 1,4,5,8-naphthalene diimide (NDI) units connected in a head-to-tail fashion by flexible peptide linkers. Previously, a threading tetraintercalator composed of alternating minor–major–minor groove-binding modules was shown to bind specifically to a 14 bp DNA sequence with a dissociation half-life of 16 days [Holman, G. G., et al. (2011) Nat. Chem. 3, 875–881]. Herein are described new NDI-based tetraintercalators with a different major groove-binding module and a reversed N to C directionality of one of the minor groove-binding modules. DNase I footprinting and kinetic analyses revealed that these new tetraintercalators are able to discriminate, by as much as 30-fold, 14 bp DNA binding sites that differ by 1 or 2 bp. Relative affinities were found to correlate strongly with dissociation rates, while overall C2 symmetry in the DNA-binding molecule appeared to contribute to enhanced association rates.
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影响因子：
15
作者：
Guelev, V;Sorey, S;Iverson, BL
通讯作者：
Iverson, BL
DOI：
10.1073/pnas.0909192106
发表时间：
2009-09-29
影响因子：
11.1
作者：
Muzikar, Katy A.;Nickols, Nicholas G.;Dervan, Peter B.
通讯作者：
Dervan, Peter B.
影响因子：
56.9
作者：
MOSER, HE;DERVAN, PB
通讯作者：
DERVAN, PB
影响因子：
3.5
作者：
Murr, MM;Harting, MT;Iverson, BL
通讯作者：
Iverson, BL
影响因子：
2.1
作者：
Eggen, IF;Bakelaar, FT;Ter Voert, EJM
通讯作者：
Ter Voert, EJM