迈向1:1聚酰胺:DNA识别的规则。
Toward rules for 1:1 polyamide:DNA recognition.
作者信息
Urbach A R, Dervan P B
机构信息
Division of Chemistry and Chemical Engineering, 164-30, California Institute of Technology, Pasadena, CA 91125, USA.
出版信息
Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4343-8. doi: 10.1073/pnas.081070798.
Polyamides composed of four amino acids, imidazole (Im), pyrrole (Py), hydroxypyrrole (Hp), and beta-alanine (beta), are synthetic ligands that form highly stable complexes in the minor groove of DNA. Although specific pairing rules within the 2:1 motif can be used to distinguish the four Watson. Crick base pairs, a comparable recognition code for 1:1 polyamide:DNA complexes had not been described. To set a quantitative baseline for the field, the sequence specificities of Im, Py, Hp, and beta for the four Watson. Crick base pairs were determined for two polyamides, Im-beta-ImPy-beta-Im-beta-ImPy-beta-Dp (1, for Im, Py, and beta) and Im-beta-ImHp-beta-Im-beta-ImPy-beta-Dp (2, for Hp), in a 1:1 complex within the DNA sequence context 5'-AAAGAGAAGAG-3'. Im residues do not distinguish G,C from A,T but bind all four base pairs with high affinity. Py and beta residues exhibit > or = 10-fold preference for A,T over G,C base pairs. The Hp residue displays a unique preference for a single A.T base pair with an energetic penalty.
由四种氨基酸（咪唑（Im）、吡咯（Py）、羟基吡咯（Hp）和β-丙氨酸（β））组成的聚酰胺是在DNA小沟中形成高度稳定复合物的合成配体。尽管2:1基序内的特定配对规则可用于区分四种沃森-克里克碱基对，但尚未描述1:1聚酰胺与DNA复合物的类似识别密码。为该领域设定一个定量基线，在DNA序列5'-AAAGAGAAGAG-3'的1:1复合物中，确定了两种聚酰胺（Im-β-ImPy-β-Im-β-ImPy-β-Dp（1，针对Im、Py和β）和Im-β-ImHp-β-Im-β-ImPy-β-Dp（2，针对Hp））中Im、Py、Hp和β对四种沃森-克里克碱基对的序列特异性。Im残基不能区分G、C与A、T，但能以高亲和力结合所有四种碱基对。Py和β残基对A、T碱基对的偏好比对G、C碱基对高≥10倍。Hp残基对单个A·T碱基对表现出独特的偏好，但存在能量代价。
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