| Reference | [1]. J Org Chem. 2018 Aug 17;83(16):8851-8862. doi: 10.1021/acs.joc.8b01002. Epub 2018 Jul 27.<br />
Synthesis and Properties of 2'-OMe-RNAs Modified with Cross-Linkable 7-Deazaguanosine Derivatives.<br />
Yamada K(1), Abe Y(1), Murase H(1), Ida Y(1), Hagihara S(1), Nagatsugi F(1).<br />
Author information: (1)Institute of Multidisciplinary Research for Advanced Materials (IMRAM) , Tohoku University , 2-1-1 Katahira , Aoba-ku, Sendai-shi 980-8577 , Japan.<br />
Cross-linkable 7-deaza-6-vinylguanosine (ADVP) and 7-propynyl-7-deaza-6-vinylguanosine (ADpVP) derivatives were synthesized and successfully incorporated into 2'-OMe-RNA oligonucleotides by solid-phase oligonucleotide synthesis. Analysis of their cross-link properties revealed that the 7-propynyl substituent on ADpVP induces a significant enhancement of the cross-link kinetics of the proximal 6-vinyl group to the complementary uracil base in the target RNA compared to that of ADVP. In addition, the 2'-OMe-RNA oligonucleotide containing ADpVP exhibited a higher antisense effect on luciferase production in the cell lysate than that of ADVP. These results suggested that the 7-substituted 7-deaza-6-vinylguanosine derivatives can be used as potent cross-linkers to target mRNA inside of cells.<br />
DOI: 10.1021/acs.joc.8b01002 PMID: 30014695<br />
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[2]. Bioorg Chem. 2003 Feb;31(1):24-43. doi: 10.1016/s0045-2068(02)00513-8.<br />
Biosynthesis of the 7-deazaguanosine hypermodified nucleosides of transfer RNA.<br />
Iwata-Reuyl D(1).<br />
Author information: (1)Department of Chemistry, Portland State University, P.O. Box 751, Portland, OR 97201, USA. [email protected]<br />
Transfer RNA (tRNA) is structurally unique among nucleic acids in harboring an astonishing diversity of post-transcriptionally modified nucleoside. Two of the most radically modified nucleosides known to occur in tRNA are queuosine and archaeosine, both of which are characterized by a 7-deazaguanosine core structure. In spite of the phylogenetic segregation observed for these nucleosides (queuosine is present in Eukarya and Bacteria, while archaeosine is present only in Archaea), their structural similarity suggested a common biosynthetic origin, and recent biochemical and genetic studies have provided compelling evidence that a significant portion of their biosynthesis may in fact be identical. This review covers current understanding of the physiology and biosynthesis of these remarkable nucleosides, with particular emphasis on the only two enzymes that have been discovered in the pathways: tRNA-guanine transglycosylase (TGT), which catalyzes the insertion of a modified base into the polynucleotide with the concomitant elimination of the genetically encoded guanine in the biosynthesis of both nucleosides, and S-adenosylmethionine:tRNA ribosyltransferase-isomerase (QueA), which catalyzes the penultimate step in the biosynthesis of queuosine, the construction of the carbocyclic side chain.<br />
DOI: 10.1016/s0045-2068(02)00513-8 PMID: 12697167<br />
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[3]. Chem Biodivers. 2010 Oct;7(10):2616-21. doi: 10.1002/cbdv.201000239.<br />
Efficient synthesis of the tRNA nucleoside preQ0, 7-cyano-7-deazaguanosine, via microwave-assisted iodo→carbonitrile exchange.<br />
Ming X(1), Seela F.<br />
Author information: (1)Laboratory of Bioorganic Chemistry and Chemical Biology, Center for Nanotechnology, Heisenbergstrasse 11, D-48149 Münster, Germany.<br />
The naturally occurring tRNA nucleoside preQ(0), 7-cyano-7-deazaguanosine, which is a central intermediate for other natural occurring 7-deazapurine nucleosides was synthesized via a copper(I)-ion-mediated iodo→carbonitrile exchange. The reaction was performed on the easily accessible 7-iodo-7-deazaguanosine under microwave conditions. The overall reaction yield was 30% starting with the glycosylation reaction of the nucleobase. Corresponding 2'-deoxyribonucleosides were prepared following the same route.<br />
DOI: 10.1002/cbdv.201000239 PMID: 20963777<br />
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[4]. Antiviral Res. 1995 Mar;26(2):203-9. doi: 10.1016/0166-3542(94)00084-l.<br />
Broad-spectrum activity of 8-chloro-7-deazaguanosine against RNA virus infections in mice and rats.<br />
Smee DF(1), Alaghamandan HA, Ramasamy K, Revankar GR.<br />
Author information: (1)ICN Nucleic Acid Research Institute, Costa Mesa, CA 92626, USA.<br />
A novel nucleoside analog, 8-chloro-7-deazaguanosine (8-Cl-7-dzGuo), was evaluated for anti-RNA virus activity in rodents in parallel with the related compound 7-deaza-7-thia-8-oxoguanosine (7-dzTOGuo). Half-daily intraperitoneal (i.p.) doses of each substance administered 24 and 18 h prior to i.p. virus challenge protected the majority of mice infected with banzi, encephalomyocarditis, San Angelo, and Semliki Forest viruses at doses of 25, 50 and 100 mg/kg/day. These compounds at 100 mg/kg/day also protected most suckling rats infected intranasally with rat coronavirus. However, no survival benefit was afforded to treated mice infected intranasally with vesicular stomatitis virus. 8-Cl-7-dzguo was orally active against Semliki Forest virus in mice at 200 and 400 mg/kg/day, whereas 7-dzTOGuo is reported to not be effective orally. In uninfected mice, the two compounds induced similar amounts of interferon following i.p. injections. Interferon was induced by oral treatments with 8-Cl-7-dzGuo but not with 7-dzTOGuo. Fifty percent acute lethal doses to uninfected mice treated i.p. in half-daily doses for one day with 7-deazaguanosine (7-dzGuo), 7-dzTOGuo, and 8-Cl-7-dzGuo were 400, 600 and > 1600 (no mortality at this dose) mg/kg/day, respectively. Daily, i.p. treatments for 14 days with these substances (100 mg/kg/day) showed 7-dzGuo as 100% lethal and the other two substances as not toxic. By virtue of reduced toxicity and oral bioavailability, 8-Cl-7-dzGuo appears to have the greatest clinical potential as an interferon-inducing antiviral agent.<br />
DOI: 10.1016/0166-3542(94)00084-l PMCID: PMC7125532 PMID: 7605116<br />
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[5]. Antimicrob Agents Chemother. 1991 Jan;35(1):152-7. doi: 10.1128/AAC.35.1.152.<br />
Immunoenhancing properties and antiviral activity of 7-deazaguanosine in mice.<br />
Smee DF(1), Alaghamandan HA, Gilbert J, Burger RA, Jin A, Sharma BS, Ramasamy K, Revankar GR, Cottam HB, Jolley WB, et al.<br />
Author information: (1)Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan 84322-5600.<br />
The nucleotide analog 7-deazaguanosine has not previously been reported to possess biological (antiviral or antitumor) properties in cell culture or in vivo. Up to 10(5) U of interferon per ml was detected in mouse sera 1 to 4 h following oral (200-mg/kg of body weight) and intraperitoneal (50-mg/kg) doses of the compound. 7-Deazaguanosine also caused significant activation of natural killer and phagocytic cells but did not augment T- and B-cell blastogenesis. Intraperitoneal treatments of 50, 100, and 200 mg/kg/day administered 24 and 18 h before virus inoculation were highly protective in mice inoculated with lethal doses of Semliki Forest or San Angelo viruses. Less but still significant survivor increases were evident in treated mice infected with banzi or encephalomyocarditis viruses. In most cases, the degree of antiviral activity was similar to that exhibited by the biological response modifier 7-thia-8-oxoguanosine. 7-Thia-8-oxoguanosine was more potent than 7-deazaguanosine against encephalomyocarditis virus in mice, however. Oral efficacy was achieved with 7-deazaguanosine treatments of greater than or equal to 100 mg/kg against all virus infections, whereas 7-thia-8-oxoguanosine is reported to be devoid of oral activity in rodents. Thus, 7-deazaguanosine represents the first reported orally active nucleoside biological response modifier exhibiting broad-spectrum antiviral activity against particular types of RNA viruses.<br />
DOI: 10.1128/AAC.35.1.152 PMCID: PMC244957 PMID: 1707603
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