Nuclease stability as dominant factor in the antiviral activity of oligonucleotides directed against HSV-1 IE110
The anti-herpes simplex virus type 1 (anti-HSV-1) efficacy of a series of oligonucleotides was determined as a function of their chemical structure. All oligonucleotides consisted of the same sequence directed against the translation initiation codon of the HSV-1 immediate early gene. The oligonucle...
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Veröffentlicht in: | Antiviral research 1997, Vol.33 (2), p.135-139 |
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container_title | Antiviral research |
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creator | Peyman, Anusch Helsberg, Matthias Kretzschmar, Gerhard Mag, Matthias Ryte, Antonina Uhlmann, Eugen |
description | The anti-herpes simplex virus type 1 (anti-HSV-1) efficacy of a series of oligonucleotides was determined as a function of their chemical structure. All oligonucleotides consisted of the same sequence directed against the translation initiation codon of the HSV-1 immediate early gene. The oligonucleotides were modified with phosphorothioate linkage patterns according to various protection strategies against nucleolytic degradation. We show that nuclease resistance is the dominant factor that determines the antiviral efficacy in this series. A minimal protection strategy, consisting of end-capping and pyrimidine protection, has proven to be particularly useful, because it not only yields nuclease-resistant oligonucleotides but also minimizes non-sequence-specific effects. |
doi_str_mv | 10.1016/S0166-3542(96)01003-0 |
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All oligonucleotides consisted of the same sequence directed against the translation initiation codon of the HSV-1 immediate early gene. The oligonucleotides were modified with phosphorothioate linkage patterns according to various protection strategies against nucleolytic degradation. We show that nuclease resistance is the dominant factor that determines the antiviral efficacy in this series. A minimal protection strategy, consisting of end-capping and pyrimidine protection, has proven to be particularly useful, because it not only yields nuclease-resistant oligonucleotides but also minimizes non-sequence-specific effects.</description><identifier>ISSN: 0166-3542</identifier><identifier>EISSN: 1872-9096</identifier><identifier>DOI: 10.1016/S0166-3542(96)01003-0</identifier><identifier>PMID: 9021055</identifier><identifier>CODEN: ARSRDR</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antisense ; Antiviral agents ; Antiviral Agents - pharmacology ; Biological and medical sciences ; Cercopithecus aethiops ; Deoxyribonucleases - metabolism ; Herpes simplex virus ; Herpesvirus 1, Human - drug effects ; Humans ; Medical sciences ; Nuclease resistance ; Oligodeoxyribonucleotides - chemistry ; Oligodeoxyribonucleotides - pharmacology ; Oligonucleotide inhibition ; Partial modification ; Pharmacology. 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All oligonucleotides consisted of the same sequence directed against the translation initiation codon of the HSV-1 immediate early gene. The oligonucleotides were modified with phosphorothioate linkage patterns according to various protection strategies against nucleolytic degradation. We show that nuclease resistance is the dominant factor that determines the antiviral efficacy in this series. A minimal protection strategy, consisting of end-capping and pyrimidine protection, has proven to be particularly useful, because it not only yields nuclease-resistant oligonucleotides but also minimizes non-sequence-specific effects.</description><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antisense</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cercopithecus aethiops</subject><subject>Deoxyribonucleases - metabolism</subject><subject>Herpes simplex virus</subject><subject>Herpesvirus 1, Human - drug effects</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Nuclease resistance</subject><subject>Oligodeoxyribonucleotides - chemistry</subject><subject>Oligodeoxyribonucleotides - pharmacology</subject><subject>Oligonucleotide inhibition</subject><subject>Partial modification</subject><subject>Pharmacology. 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Antiinfectious agents. Antiparasitic agents</topic><topic>Antisense</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cercopithecus aethiops</topic><topic>Deoxyribonucleases - metabolism</topic><topic>Herpes simplex virus</topic><topic>Herpesvirus 1, Human - drug effects</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Nuclease resistance</topic><topic>Oligodeoxyribonucleotides - chemistry</topic><topic>Oligodeoxyribonucleotides - pharmacology</topic><topic>Oligonucleotide inhibition</topic><topic>Partial modification</topic><topic>Pharmacology. 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All oligonucleotides consisted of the same sequence directed against the translation initiation codon of the HSV-1 immediate early gene. The oligonucleotides were modified with phosphorothioate linkage patterns according to various protection strategies against nucleolytic degradation. We show that nuclease resistance is the dominant factor that determines the antiviral efficacy in this series. A minimal protection strategy, consisting of end-capping and pyrimidine protection, has proven to be particularly useful, because it not only yields nuclease-resistant oligonucleotides but also minimizes non-sequence-specific effects.</abstract><cop>Amsterdam</cop><pub>Elsevier B.V</pub><pmid>9021055</pmid><doi>10.1016/S0166-3542(96)01003-0</doi><tpages>5</tpages></addata></record> |
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subjects | Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antisense Antiviral agents Antiviral Agents - pharmacology Biological and medical sciences Cercopithecus aethiops Deoxyribonucleases - metabolism Herpes simplex virus Herpesvirus 1, Human - drug effects Humans Medical sciences Nuclease resistance Oligodeoxyribonucleotides - chemistry Oligodeoxyribonucleotides - pharmacology Oligonucleotide inhibition Partial modification Pharmacology. Drug treatments Protection pattern Structure-Activity Relationship Vero Cells |
title | Nuclease stability as dominant factor in the antiviral activity of oligonucleotides directed against HSV-1 IE110 |
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