Abstract
Methods for stabilizing G-quadruplex formation is a promising therapeutic approach for cancer treatment and other biomedical applications because stable G-quadruplexes efficiently inhibit biological reactions. Oligo and polyethylene glycols are promising biocompatible compounds, and we have shown that linear oligoethylene glycols can stabilize G-quadruplexes. Here, we developed a new modified deoxythymine with dibranched or tribranched tetraethylene glycol (TEG) and incorporated these TEG-modified deoxythymines into a loop region that forms an antiparallel G-quadruplex. We analyzed the stability of the modified G-quadruplexes, and the results showed that the tribranched TEG destabilized G-quadruplexes through entropic contributions, likely through steric hindrance. Interestingly, the dibranched TEG modification increased G-quadruplex stability relative to the unmodified DNA structures due to favorable enthalpic contributions. Molecular dynamics calculations suggested that dibranched TEG interacts with the G-quadruplex through hydrogen bonding and CH-π interactions. Moreover, these branched TEG-modified deoxythymine protected the DNA oligonucleotides from degradation by various nucleases in human serum. By taking advantage of the unique interactions between DNA and branched TEG, advanced DNA materials can be developed that affect the regulation of DNA structure.
Highlights
Methods for controlling biological reactions relevant to disease are very useful in therapeutic and medical applications [1]
We evaluated the effect of tetraethylene glycol on G-quadruplex stability
G-rich sequences show a significant degree of structural polymorphism, the thrombin aptamer sequence reliably folds into an antiparallel G-quadruplex that melts in a two-state manner
Summary
Methods for controlling biological reactions relevant to disease are very useful in therapeutic and medical applications [1]. It has been reported that biological reactions such as transcription, translation, and telomerase elongation are inhibited by stable G-quadruplex formation in target genes [1,4,5,6]. Molecules 2020, 25, 705 the G-quadruplex structure have been developed, such as 5,10,15,20-tetrakis-(N-methyl-4-pyridyl) porphyrin, berberine, and N-methyl mesoporphyrin IX [7,8,9]. These G-quadruplex-stabilizing compounds stabilize duplex structures to some extent. Simple and selective compounds that enable sequence-specific control of
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