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G‐Quadruplexes with Tetra(ethylene glycol)‐Modified Deoxythymidines are Resistant to Nucleases and Inhibit HIV‐1 Reverse Transcriptase
Author(s) -
TateishiKarimata Hisae,
Muraoka Takahiro,
Kinbara Kazushi,
Sugimoto Naoki
Publication year - 2016
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600162
Subject(s) - reverse transcriptase , oligonucleotide , dna , ethylene glycol , chemistry , g quadruplex , combinatorial chemistry , rna , microbiology and biotechnology , biology , biochemistry , gene , organic chemistry
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.