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Peptides Selected by G4-mRNA Display-Seq Enable RNA G-Quadruplex Recognition and Gene Regulation
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2023-08-15 , DOI: 10.1021/jacs.3c04534
Xi Mou 1 , Chun Kit Kwok 1, 2
Journal of the American Chemical Society ( IF 14.4 ) Pub Date : 2023-08-15 , DOI: 10.1021/jacs.3c04534
Xi Mou 1 , Chun Kit Kwok 1, 2
Affiliation
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G-quadruplexes (G4s) are noncanonical secondary structures that play critical roles in both chemistry and biology. Although several approaches have been developed for G4 targeting, such as chemicals and antibodies, there is currently no general and efficient platform for G4-specific peptides. In this study, we developed a new platform, G4-mRNA display-Seq, for selecting peptides that specifically recognize the G4 target of interest. By using an RNA G4 (rG4) found in human telomerase RNA (hTERC) as the target, we have identified a novel short peptide, namely, peptide 11 (pep11), which displays high affinity and selectivity to hTERC rG4. Furthermore, we designed tandem and cyclic versions of pep11 and found that both modified versions exhibit stronger binding affinity with preferential rG4 selectivity. Notably, we have demonstrated that these peptides can negatively regulate gene expression by targeting rG4. Our results provide a universal platform for the discovery of G4-targeting peptides and demonstrate the ability of these peptides to regulate G4-mediated gene functions.
中文翻译:
G4-mRNA Display-Seq 选择的肽可实现 RNA G 四链体识别和基因调控
G-四链体 (G4) 是非常规二级结构,在化学和生物学中发挥着关键作用。尽管已经开发了多种针对 G4 靶向的方法,例如化学品和抗体,但目前还没有针对 G4 特异性肽的通用且有效的平台。在本研究中,我们开发了一个新平台 G4-mRNA 显示序列,用于选择特异性识别感兴趣的 G4 靶标的肽。通过使用人端粒酶RNA(hTERC)中发现的RNA G4(rG4)作为靶标,我们鉴定了一种新型短肽,即肽11(pep11),它对hTERC rG4表现出高亲和力和选择性。此外,我们设计了 pep11 的串联和循环版本,发现两种修饰版本都表现出更强的结合亲和力和优先的 rG4 选择性。值得注意的是,我们已经证明这些肽可以通过靶向 rG4 来负向调节基因表达。我们的结果为发现 G4 靶向肽提供了一个通用平台,并证明了这些肽调节 G4 介导的基因功能的能力。
更新日期:2023-08-15
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
G4-mRNA Display-Seq 选择的肽可实现 RNA G 四链体识别和基因调控
G-四链体 (G4) 是非常规二级结构,在化学和生物学中发挥着关键作用。尽管已经开发了多种针对 G4 靶向的方法,例如化学品和抗体,但目前还没有针对 G4 特异性肽的通用且有效的平台。在本研究中,我们开发了一个新平台 G4-mRNA 显示序列,用于选择特异性识别感兴趣的 G4 靶标的肽。通过使用人端粒酶RNA(hTERC)中发现的RNA G4(rG4)作为靶标,我们鉴定了一种新型短肽,即肽11(pep11),它对hTERC rG4表现出高亲和力和选择性。此外,我们设计了 pep11 的串联和循环版本,发现两种修饰版本都表现出更强的结合亲和力和优先的 rG4 选择性。值得注意的是,我们已经证明这些肽可以通过靶向 rG4 来负向调节基因表达。我们的结果为发现 G4 靶向肽提供了一个通用平台,并证明了这些肽调节 G4 介导的基因功能的能力。