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
Hauptverfasser: Peyman, Anusch, Helsberg, Matthias, Kretzschmar, Gerhard, Mag, Matthias, Ryte, Antonina, Uhlmann, Eugen
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container_end_page 139
container_issue 2
container_start_page 135
container_title Antiviral research
container_volume 33
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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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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