Journal
JOURNAL OF MOLECULAR LIQUIDS
Volume 383, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.molliq.2023.122071
Keywords
Base modified DNA; Helical parameter; Z -DNA; DNA dynamics; NMR
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Developing chemical modifications of DNA to find drug targets is challenging. In this study, double-methylated guanosine was incorporated into DNA and its solution structure was determined. The flexible Z-DNA formed as a result showed slow conformational exchange and a novel helical structure. The transition from Z-DNA to tBZ provides new insights into structural diversity and may serve as a potential drug target.
Developing chemical modifications of DNA to find drug targets is challenging. Here, we incorporated doublemethylated guanosine into a DNA duplex and determined its solution structure using NMR and restrained molecular dynamics. The double-methylation of guanosine promotes aberrantly distorted Z-DNA with a widened groove space. This flexible Z-DNA exhibited slow conformational exchange (second time-scale) with a novel helical structure (denoted as tBZ-form). We find three characteristics of the Z-to-tBZ transition: 1) syn-to-syn glycosidic conformation (Z-to-non-B); 2) loss of left-handedness (that is, Z-to-non-Z); 3) entropic gain of the Z-totBZ transition. We anticipate that this flexible Z-DNA can be considered a novel target for drug discovery and that the Z-to-tBZ transition will provide new insights into structural diversity.
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