Binding of helix-threading peptides to E-coli 16S ribosomal RNA and inhibition of the S15-16S complex
Binding of helix-threading peptides to E-coli 16S ribosomal RNA and inhibition of the S15-16S complex
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DOI：
10.1002/cbic.200500285
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发表时间：
2005-12-01
期刊：
影响因子：
3.2
通讯作者：
Beal, PA
中科院分区：
文献类型：
--
作者：
Gooch, BD;Krishnamurthy, M;Beal, PA
螺旋穿线肽（Helix-threading peptides，HTPs）是一类新的小分子，其选择性地结合到邻近螺旋缺陷的双链RNA结构上，并将肽功能投射到不同的双链凹槽中。为了进一步探索和开发HTP设计选择性结合RNA的能力，我们将原核核糖体RNA 16 S的螺旋22鉴定为靶标。该螺旋是核糖体蛋白S15结合位点的组成部分。此外，S15- 16 S RNA相互作用对于细菌核糖体的有序组装是重要的。在这里，我们提出的螺旋线程肽的合成和表征，选择性结合到螺旋22的E。coli 16S RNA。这些化合物通过将N末端置于小沟中并将C末端置于大沟中的螺纹嵌入来结合螺旋22。结合依赖于RNA中高度保守的富含嘌呤的内环的存在，而环的去除对经典内插剂溴化乙锭和丙基甲锭-EDTA的结合影响最小。Fe（（MPEFe）-Fe-.）。此外，结合选择性转化为选择性抑制S1 S-16 S复合物的形成。
Helix-threading peptides (HTPs) constitute a new class of small molecules that bind selectively to duplex RNA structures adjacent to helix defects and project peptide functionality into the dissimilar duplex grooves. To further explore and develop the capabilities of the HTP design for binding RNA selectively, we identified helix 22 of the prokoryotic ribosomal RNA 16S as a target. This helix is a component of the binding site for the ribosomal protein S15. In addition, the S15-16S RNA interaction is important for the ordered assembly of the bacterial ribosome. Here we present the synthesis and characterization of helix-threading peptides that bind selectively to helix 22 of E. coli 16S RNA. These compounds bind helix 22 by threading intercalation placing the N termini in the minor groove and the C termini in the major groove. Binding is dependent on the presence of a highly conserved purine-rich internal loop in the RNA, whereas removal of the loop minimally affects binding of the classical intercolators ethidium bromide and methidiumpropyi-EDTA(.)Fe ((MPEFe)-Fe-.). Moreover, binding selectivity translates into selective inhibition of formation of the S1S-16S complex.