State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, P. R. China.
Chem Commun (Camb). 2020 Jun 18;56(48):6567-6570. doi: 10.1039/d0cc02102d. Epub 2020 May 12.
A dual-functional peptide-PNA (peptide nucleic acid) conjugate consisting of a PNA G3-tract and an RHAU23 peptide is devised to target nucleic acids bearing three tandem guanine tracts (G-tracts). The PNA G3-tract joins the three G-tracts to form a stable bimolecular G-quadruplex (G4) and the resulting G4 is then bound by the RHAU23 moiety to form an extra stable G4-peptide complex. Owing to this synergistic dual structural enforcement, the conjugate accomplished extremely high selectivity and nM to sub-nM affinities towards its targets that are up to 1000 times greater than the small molecule G4 ligands. As a result, the conjugate impacts the tracking activity of motor proteins on DNA with superior selectivity and potency that are rarely seen in other G4-targeting approaches.
设计了一种由 PNA G3 链段和 RHAU23 肽组成的双功能肽-PNA（肽核酸）缀合物，以靶向含有三个串联鸟嘌呤链段（G 链段）的核酸。PNA G3 链段将三个 G 链段连接起来，形成稳定的双分子 G-四链体（G4），然后 RHAU23 部分与形成的 G4 结合，形成额外稳定的 G4-肽复合物。由于这种协同的双重结构强化，该缀合物对其靶标表现出极高的选择性和纳摩尔至亚纳摩尔亲和力，比小分子 G4 配体高 1000 倍以上。结果，该缀合物对 DNA 上的马达蛋白的追踪活性具有优异的选择性和效力，这在其他 G4 靶向方法中很少见。
