Solid-phase synthesis of DNA binding polyamides on oxime resin
Solid-phase synthesis of DNA binding polyamides on oxime resin
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DOI：
10.1016/s0968-0896(02)00133-5
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发表时间：
2002-08-01
影响因子：
3.5
通讯作者：
Dervan, PB
中科院分区：
文献类型：
--
作者：
Belitsky, JM;Nguyen, DH;Dervan, PB
控制DNA结合聚酰胺的能量学和特异性是抑制蛋白质-DNA复合物形成和基因调控研究的必要条件。通常，使用Boc单体的固相合成方法依赖于Boc- β -ala - pam树脂，该树脂在与N，N-二甲氨基丙胺（Dp）裂解后，在c端提供β -丙氨酸-Dp尾部。为了解决这种尾部对DNA小槽结合的能量后果，我们描述了一种采用Kaiser肟树脂的替代固相方法，该方法允许合成具有逐渐缩短的c端尾部的聚酰胺。没有Dp和具有甲基酰胺尾部而不是β -丙氨酸尾部的聚酰胺相对于标准β -Dp尾部表现出相似的亲和力。截断的尾部减少了β - dp尾部的A，T碱基对能量偏好，这将允许更多种类的DNA序列被发夹聚酰胺靶向。(C) 2002 Elsevier Science Ltd.版权所有。
Control of the energetics and specificity of DNA binding polyamides is necessary for inhibition of protein-DNA complex formation and gene regulation studies. Typically, solid-phase methods using Boc monomers for synthesis have depended on Boc-beta-Ala-PAM resin which affords a beta-alanine-Dp tail at the C-terminus, after cleavage with N,N-dimethylaminopropylamine (Dp). To address the energetic consequences of this tail for DNA minor groove binding, we describe an alternative solid phase method employing the Kaiser oxime resin which allows the synthesis of polyamides with incrementally shortened C-terminal tails. Polyamides without Dp and having methyl amide tails rather than beta-alanine show similar affinity relative to the standard beta-Dp tail. The truncated tail diminishes the A,T base pair energetic preference of the beta-Dp tail which will allow a greater variety of DNA sequences to be targeted by hairpin polyamides. (C) 2002 Elsevier Science Ltd. All rights reserved.