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Templates direct the sequence-specific anchoring of the C-terminus of peptido RNAs
Chemical Science ( IF 8.4 ) Pub Date : 2020/03/02 , DOI: 10.1039/c9sc05958j
Biswarup Jash 1, 2, 3, 4 , Clemens Richert 1, 2, 3, 4
Affiliation  

When amino acids and ribonucleotides react in aqueous condensation buffer, they form peptido RNA with a phosphoramidate bond between the N-terminus of the peptide and the 5′-terminal phosphate of a ribonucleotide. If peptido RNA was the product of spontaneous reactions of amino acids and nucleotides, there must have been a transition to peptidyl tRNAs, where the C-terminus of the peptide is ester-linked to the 2′,3′-terminus of an oligonucleotide. Here we report how short peptido RNAs react with the 3′-terminus of oligodeoxynucleotides, templated by RNA strands. In our model system, the rate and yield of the anchoring of the C-terminus of the dipeptido dinucleotides to an amino group was found to depend on the sequence of the peptide, the 5′-terminal nucleotide of the dinucleotide and the RNA template. In all cases tested, highest yields were found for dinucleotides hybridizing next to the primer terminus. For the most reactive species, GlyPro-AA, anchoring yields ranged from 8–99%, depending on the template. When LeuLeu-AA, PhePhe-AA and GlyGly-AA were allowed to compete for anchoring on 3′-UUC-5′ as templating sequence, they gave a product ratio of 1 : 2 : 6, and this selectivity was almost independent of the terminal base of the primer. Our results show the control that a simple duplex context has over the covalent anchoring of peptido RNAs at a position known from peptidyl tRNAs. Processes of this type may have bridged the gap between untemplated condensation reactions and the highly specific processes of ribosomal protein synthesis.

中文翻译:

模板指导肽RNA的C端的序列特异性锚定

当氨基酸和核糖核苷酸在水性缩合缓冲液中反应时,它们形成在肽的N端与核糖核苷酸的5'-末端磷酸酯之间具有氨基磷酸酯键的肽RNA。如果肽RNA是氨基酸和核苷酸自发反应的产物,则必须已经过渡到肽基tRNA,其中肽的C端与寡核苷酸的2',3'端酯连接。在这里,我们报告了短肽RNA如何与RNA链模板化的寡脱氧核苷酸的3'-末端反应。在我们的模型系统中,C锚固的速率和产量发现二肽基二核苷酸与氨基的末端取决于肽的序列,二核苷酸的5'-末端核苷酸和RNA模板。在所有测试的情况下,发现在引物末端附近杂交的二核苷酸产量最高。对于活性最高的物种,GlyPro-AA,锚固产率范围为8–99%,具体取决于模板。当LeuLe​​u-AA,PhePhe-AA和GlyGly-AA作为模板序列竞争锚定在3'-UUC-5'上时,它们的产物比为1:2:6,这种选择性几乎与底漆的末端碱基。我们的结果显示出控制,即简单的双链体环境对肽基RNA的共价锚定位于肽基tRNA已知的位置。
更新日期:2020-04-01
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