Nils Lefringhausen, Catharina Erbacher, Matthias Elinkmann, Uwe Karst and Jens Müller*,
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Highly stabilizing Ag<sup>+</sup>-mediated base pairs were formed with cytosine and guanine (i.e., <b>P</b>–Ag<sup>+</sup>–<b>C</b> and <b>P</b>–Ag<sup>+</sup>–<b>G</b> base pairs), whereas the analogous base pairs with thymine and adenine were much less stable and hence formed incompletely. Surprisingly, the intermediate formation of a homodimeric duplex of the <b>P</b>-containing oligonucleotide was observed in all cases, albeit to a different extent. The homodimer is composed of <b>P</b>–Ag<sup>+</sup>–<b>P</b> base pairs and 18 overhanging mismatched canonical nucleobases. It demonstrates the obstacles present when designing metal-mediated base pairs as metal complexation may take place irrespective of the surrounding natural base pairs. Homodimer formation was found to be particularly prominent when the designated metal-mediated base pairs are of low stability, suggesting that homodimers and regular duplexes are formed in a competing manner.</p>","PeriodicalId":29,"journal":{"name":"Bioconjugate Chemistry Bioconjugate","volume":null,"pages":null},"PeriodicalIF":4.0000,"publicationDate":"2023-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Contiguous Silver(I)-Mediated Base Pairs of Imidazophenanthroline and Canonical Nucleobases in DNA Duplexes: Formation of Classical Duplexes versus Homodimer Formation\",\"authors\":\"Nils Lefringhausen, Catharina Erbacher, Matthias Elinkmann, Uwe Karst and Jens Müller*, \",\"doi\":\"10.1021/acs.bioconjchem.3c00494\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Metal-mediated base pairs represent a topical alternative to canonical hydrogen-bonded base pairs. 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引用次数: 0
摘要
金属介导的碱基配对是典型氢键碱基配对的热门替代品。在这种情况下,配体 1H-咪唑并[4,5-f][1,10]菲罗啉(P)作为一种人工核碱基被引入到以乙二醇核酸为基础的核苷类似物的 DNA 寡核苷酸中,使寡核苷酸包含一个由六个连续的 P 残基组成的中心块。与胞嘧啶和鸟嘌呤形成的 Ag+ 介导的碱基配对具有高度稳定性(即 P-Ag+-C 和 P-Ag+-G 碱基配对),而与胸腺嘧啶和腺嘌呤形成的类似碱基配对则不太稳定,因此形成不完全。令人惊讶的是,在所有情况下都能观察到含 P 寡核苷酸的同源二聚体的中间形成,只是程度不同而已。同源二聚体由 P-Ag+-P 碱基对和 18 个悬空的不匹配的典型核碱基组成。这表明在设计金属介导的碱基对时存在障碍,因为金属复合物可能与周围的天然碱基对无关。研究发现,当指定的金属介导碱基对稳定性较低时,同源二聚体的形成尤为突出,这表明同源二聚体和常规双链是以竞争的方式形成的。
Contiguous Silver(I)-Mediated Base Pairs of Imidazophenanthroline and Canonical Nucleobases in DNA Duplexes: Formation of Classical Duplexes versus Homodimer Formation
Metal-mediated base pairs represent a topical alternative to canonical hydrogen-bonded base pairs. In this context, the ligand 1H-imidazo[4,5-f][1,10]phenanthroline (P) was introduced as an artificial nucleobase in a glycol nucleic acid-based nucleoside analogue into a DNA oligonucleotide in a way that the oligonucleotide contains a central block of six contiguous P residues. The ability to engage in Ag+-mediated base pairing was evaluated with respect to the four canonical nucleosides in positions complementary to P. Highly stabilizing Ag+-mediated base pairs were formed with cytosine and guanine (i.e., P–Ag+–C and P–Ag+–G base pairs), whereas the analogous base pairs with thymine and adenine were much less stable and hence formed incompletely. Surprisingly, the intermediate formation of a homodimeric duplex of the P-containing oligonucleotide was observed in all cases, albeit to a different extent. The homodimer is composed of P–Ag+–P base pairs and 18 overhanging mismatched canonical nucleobases. It demonstrates the obstacles present when designing metal-mediated base pairs as metal complexation may take place irrespective of the surrounding natural base pairs. Homodimer formation was found to be particularly prominent when the designated metal-mediated base pairs are of low stability, suggesting that homodimers and regular duplexes are formed in a competing manner.
期刊介绍:
Bioconjugate Chemistry invites original contributions on all research at the interface between man-made and biological materials. The mission of the journal is to communicate to advances in fields including therapeutic delivery, imaging, bionanotechnology, and synthetic biology. Bioconjugate Chemistry is intended to provide a forum for presentation of research relevant to all aspects of bioconjugates, including the preparation, properties and applications of biomolecular conjugates.