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

G-Quadruplexes with Tetra(ethylene glycol)-Modified Deoxythymidines are Resistant to Nucleases and Inhibit HIV-1 Reverse Transcriptase.
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Tateishi-Karimata H, Muraoka T, Kinbara K, Sugimoto N,


Tateishi-Karimata H, Muraoka T, Kinbara K, Sugimoto N, (click to view)

Tateishi-Karimata H, Muraoka T, Kinbara K, Sugimoto N,

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Chembiochem : a European journal of chemical biology 2016 07 0417(15) 1399-402 doi 10.1002/cbic.201600162

Abstract

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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