Journal Article G-Quadruplexes with Tetra(ethylene glycol)-Modified Deoxythymidines are Resistant to Nucleases and Inhibit HIV-1 Reverse Transcriptase

村岡, 貴博  ,  Muraoka, Takahiro  ,  金原, 数  ,  Kinbara, Kazushi

17 ( No. 15 )  , pp.1399 - 1402 , 2016-07 , Wiley
G-quadruplex formation in virally encoded templates arrests reverse transcription. Methods to stabilize this structure are promising for antiviral approaches. To stabilize G-quadruplex formation, deoxythymidines were modified with tetra(ethylene glycol) (TEG). The TEG-modified G-quadruplexes were stabilized significantly relative to unmodified DNA. In the presence of a TEG-modified oligonucleotide that is capable of forming an intermolecular G-quadruplex with a template containing a hu- man immunodeficiency virus-1 sequence, reverse transcription was inhibited by more than 70 % relative to the reaction in the absence of the TEG-modified oligonucleotide. Moreover, the TEG-modified deoxythymidines protected the DNA oligonucleotide from degradation by various nucleases in human serum. Thus, DNA oligonucleotides modified with TEG have potential in therapeutic applications.

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