title: G-Quadruplexes with Tetra(ethylene glycol)-Modified Deoxythymidines are Resistant to Nucleases and Inhibit HIV-1 Reverse Transcriptase.
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.
authors.affiliation: Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
authors.forename: Hisae
authors.initials: H
authors.lastname: Tateishi-Karimata
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama, 226-8503, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Muraoka
authors.affiliation: Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama, 226-8503, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Kinbara
authors.affiliation: Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, 7-1-20, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan. sugimoto@konan-u.ac.jp.|Graduate School of Frontiers of Innovative Research in Science and Technology (FIRST), Konan University, 7-1-20, Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan. sugimoto@konan-u.ac.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sugimoto
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry; D003851:Deoxyribonucleases / Q000378:metabolism; D004355:Drug Stability; D019855:Ethylene Glycol / Q000737:chemistry; D054856:G-Quadruplexes; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors*; D006801:Humans; D009841:Oligonucleotides / Q000737:chemistry / Q000494:pharmacology; D048348:Reverse Transcription / Q000187:drug effects*; D013936:Thymidine / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000998:Antiviral Agents; D009841:Oligonucleotides; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D003851:Deoxyribonucleases; D019855:Ethylene Glycol; D013936:Thymidine
keywords: DNA; G-quadruplexes; nuclease resistance; poly(ethylene glycol); reverse transcription