DESIGN OF A G-CENTER-DOT-C-SPECIFIC DNA MINOR GROOVE-BINDING PEPTIDE
DESIGN OF A G-CENTER-DOT-C-SPECIFIC DNA MINOR GROOVE-BINDING PEPTIDE
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DOI：
10.1126/science.7939719
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发表时间：
1994-10-28
期刊：
影响因子：
56.9
通讯作者：
WEMMER, DE
中科院分区：
文献类型：
--
作者：
GEIERSTANGER, BH;MRKSICH, M;WEMMER, DE
一种含有咪唑和吡咯羧胺交替的四环三肽，特异性结合DNA小凹槽中的6碱基对5‘-(A，T) gggc (A，T)-3’位点。设计的肽具有与三吡咯二霉素完全相反的特异性，它结合a，T序列。核磁共振结构研究表明，两个肽在小凹槽中以反平行的方向并排结合。在2:1配体- dna复合物中，四个咪唑中的每一个都通过氢键识别GCGC核心中的特定鸟嘌呤氨基。该合成配体靶向指定的四碱基对G-C通道，支持2:1肽-DNA基序的普遍性，用于序列特异性的DNA小槽识别。
A four-ring tripeptide containing alternating imidazole and pyrrole carboxamides specifically binds six-base pair 5'-(A,T)GCGC(A,T)-3' sites in the minor groove of DNA. The designed peptide has a specificity completely reversed from that of the tripyrrole distamycin, which binds A,T sequences. Structural studies with nuclear magnetic resonance revealed that two peptides bound side-by-side and in an antiparallel orientation in the minor groove. Each of the four imidazoles in the 2:1 ligand-DNA complex recognized a specific guanine amino group in the GCGC core through a hydrogen bond. Targeting a designated four- base pair G-C tract by this synthetic ligand supports the generality of the 2:1 peptide-DNA motif for sequence-specific minor groove recognition of DNA.