| Autor: |
Seidu YS; Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States., Roy HA; Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States., Rodgers MT; Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States. |
| Jazyk: |
angličtina |
| Zdroj: |
The journal of physical chemistry. A [J Phys Chem A] 2021 Jul 15; Vol. 125 (27), pp. 5939-5955. Date of Electronic Publication: 2021 Jul 06. |
| DOI: |
10.1021/acs.jpca.1c04303 |
| Abstrakt: |
Repetitive nucleic acid sequences, which occur in abundance throughout the mammalian genome, are of enormous research interest due to their potential to adopt fascinating and unusual molecular structures such as the i -motif. In remarkable contrast to the DNA double helix, i -motif conformations are stabilized by protonated cytosine base pairs, (Cyt)H + (Cyt), that are centrally located in the core of the i -motif and intercalated vertically in an antiparallel fashion. An in-depth understanding of how modifications influence the stability of i -motif conformations is a prerequisite to understanding their biological functions and the development of effective means of tuning their stability for specific medical and technological applications. Here, the influence of the 2'- and 3'-hydroxy substituents of the sugar moieties and 5-methylation of the cytosine nucleobases on the base-pairing interactions of protonated cytidine nucleoside analogue base pairs, ( x Cyd)H + ( x Cyd), are examined by complementary threshold collision-induced dissociation techniques and computational methods. The x Cyd nucleosides examined include the canonical DNA and RNA cytidine nucleosides, 2'-deoxycytidine (dCyd) and cytidine (Cyd), as well as several modified cytidine nucleoside analogues, 2',3'-dideoxycytidine (ddCyd), 5-methyl-2'-deoxycytidine (m 5 dCyd), and 5-methylcytidine (m 5 Cyd). Comparisons among these model base pairs indicate that the 2'- and 3'-hydroxy substituents of the sugar moieties have very little influence on the strength of the base-pairing interactions, whereas 5-methylation of the cytosine nucleobases is found to enhance the strength of the base-pairing interactions. The increase in stability resulting from 5-methylation is only modest but is more than twice as large for the DNA than RNA protonated cytidine base pair. Overall, present results suggest that canonical DNA i -motif conformations should be more stable than analogous RNA i -motif conformations and that 5-methylation of cytosine residues, a significant epigenetic marker, provides greater stabilization to DNA than RNA i -motif conformations. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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