Designed RNAs with Two Peptide-Binding Units as Artificial Templates for Native Chemical Ligation of RNA-Binding Peptides
Designed RNAs with Two Peptide-Binding Units as Artificial Templates for Native Chemical Ligation of RNA-Binding Peptides
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DOI：
10.1002/cbic.200900392
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发表时间：
2009-11-23
期刊：
影响因子：
3.2
通讯作者：
Ikawa, Yoshiya
中科院分区：
文献类型：
--
作者：
Kashiwagi, Norimasa;Yamashita, Kohei;Ikawa, Yoshiya
模板效应不仅在现代合成和酶催化中起着重要作用，而且在被认为是生命起源的关键阶段的古老的“RNA多肽（RNP）世界”中也起着重要作用。为了模拟原始模板催化的肽连接的RNA，我们以前报道的设计和合成的三元RNP复合物，其中两个肽的连接显着促进模板RNA与两个肽结合单位。然而，RNA分子也通过RNA和碱性肽之间的静电相互作用以非特异性方式促进连接反应。在这项研究中，我们抑制了这种影响，通过减少来自四膜虫内含子RNA的原始模板的长度。然而，这种修饰降低了特异性反应的模板能力。作为与原始模板一样有效的替代RNA，我们发现自二聚化RNA是一种有前途的肽连接模板，没有非特异性效应。
The template effect plays important roles not only in modern synthetic and enzymatic catalysis but also in the ancient "RNA polypeptide (RNP) world which has been postulated to be a crucial stage in the origin of life. To mimic primitive template catalysis of peptide ligations by RNAs, we previously reported the design and synthesis of a ternary RNP complex in which the ligation of two peptides was significantly facilitated by a template RNA with two peptide binding units. However, RNA molecules also promoted the ligation reaction in a nonspecific manner through electrostatic interactions between RNA and basic peptides. In this study, we suppressed this effect by reducing the length of the original template derived from the Tetrahymena intron RNA. This modification however decreased the template ability for the specific reaction. As an alternative RNA that was as effective as the original template, we found that a self dimerizing RNA was a promising template for peptide ligation without a nonspecific effect.