Abstract
A detailed understanding of the mismatched base-pairing interactions in DNA will help reveal genetic diseases and provide a theoretical basis for the development of targeted drugs. Here, we utilized mononucleotide fragment to simulate mismatch DNA interactions in a local hydrophobic microenvironment. The bipyridyl-type bridging ligands were employed as a mild stabilizer to stabilize the GG mismatch containing complexes, allowing mismatch to be visualized based on X-ray crystallography. Five single crystals of 2′-deoxyguanosine–5′–monophosphate (dGMP) metal complexes were designed and obtained via the process of self-assembly. Crystallographic studies clearly reveal the details of the supramolecular interaction between mononucleotides and guest intercalators. A novel guanine–guanine base mismatch pattern with unusual (high anti)–(high anti) type of arrangement around the glycosidic angle conformations was successfully constructed. The solution state 1H–NMR, ESI–MS spectrum studies, and UV titration experiments emphasize the robustness of this g–motif in solution. Additionally, we combined the methods of single-crystal and solution-, solid-state CD spectrum together to discuss the chirality of the complexes. The complexes containing the g–motif structure, which reduces the energy of the system, following the solid-state CD signals, generally move in the long-wave direction. These results provided a new mismatched base pairing, that is g–motif. The interaction mode and full characterizations of g–motif will contribute to the study of the mismatched DNA interaction.
Highlights
The non–B-DNA secondary structures (Afek et al, 2020; Xiong et al, 2021), which are folded in a different manner from B-DNA or form unnatural base pairs that are not used for Watson–Crick (G≡C and A T) base pairing (Watson and Crick, 1953; Brovarets’ et al, 2018), can induce genetic instability and cause a variety of human diseases (Brovarets’ et al, 2019; Li et al, 2020)
The bipyridyl-type bridging ligands with different sizes were chosen as a multifunctional auxiliary ligand; on the one hand, they can precisely adjust the orientation of purine bases through stacking interactions; on the other hand, they can provide an ideal flat, hydrophobic microenvironment with different interplanar distances for the binding of single planar aromatic molecules
They can prevent the nonenzymatic hydrolysis of nucleotide phosphate groups and increase the crystallization of nucleotide complexes, because the bridging ligands would coordinate to metal ions by competing with dGMP as a structure modifier
Summary
The non–B-DNA secondary structures (Afek et al, 2020; Xiong et al, 2021), which are folded in a different manner from B-DNA or form unnatural base pairs that are not used for Watson–Crick (G≡C and A T) base pairing (Watson and Crick, 1953; Brovarets’ et al, 2018), can induce genetic instability and cause a variety of human diseases (Brovarets’ et al, 2019; Li et al, 2020). The research of mismatched base-pairing interactions has great significance because they play an important role in various processes related to the biological function of nucleic acids (Iyer et al, 2006; Granzhan et al, 2014; Mondal et al, 2016), helping to reveal genetic diseases caused by the non–B-DNA structures. A novel guanine–guanine base mismatch pattern with unusual (high anti)—(high anti) type of arrangement around the glycosidic angle conformations was successfully constructed This base pair is different from GG Hoogsteen base pairs and reverse Watson–Crick GG mismatched base pairing (Mondal et al, 2016), but is similar to hemiprotonated CC+ and AA base pairs in i–motif and A–motif, respectively. It provides a certain theoretical basis for the development of targeted therapeutic drugs
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