Self-stabilized antisense oligodeoxynucleotide phosphorothioates: properties and anti-HIV activity.

Nucleic acids research ·Vol. 21 ·No. 11 ·1993-06-11 ·Pages 2729-35

Tang JY, Temsamani J, Agrawal S

Abstract

A new class of oligodeoxyribonucleotides has been designed, referred to here as 'self-stabilized' oligonucleotides. These oligonucleotides have hairpin loop structures at their 3' ends, and show increased resistance to degradation by snake venom phosphodiesterase, DNA polymerase I and fetal bovine serum. The self-stabilized region of the oligonucleotide does not interfere in hybridization with complementary nucleic acids as shown by melting temperature, mobility-shift and RNase H cleavage studies. Various self-stabilized oligonucleotides containing increasingly stable hairpin loop regions were studied for their anti-HIV activity. Pharmacokinetic and stability studies in mice showed increased in vivo persistence of self-stabilized oligonucleotides with respect to their linear counterparts.

MeSH Terms

Animals Antiviral Agents/chemical synthesis,chemistry,pharmacology Base Sequence Blood Cattle Cells, Cultured DNA Polymerase I/metabolism Drug Stability Genes, gag HIV-1/drug effects,physiology Humans Lymphocytes Molecular Sequence Data Nucleic Acid Conformation Nucleic Acid Hybridization Oligonucleotides, Antisense/chemical synthesis,chemistry,pharmacology Oligoribonucleotides/metabolism Phosphoric Diester Hydrolases/metabolism RNA, Viral/metabolism Ribonuclease H/metabolism Thionucleotides Virus Replication/drug effects

Chemicals

Antiviral Agents Oligonucleotides, Antisense Oligoribonucleotides RNA, Viral Thionucleotides DNA Polymerase I Ribonuclease H Phosphoric Diester Hydrolases

Authors & Affiliations

3 authors, click to expand affiliations / ORCID

Tang J Y

Hybridon, Inc., Worcester, MA 01605.

Temsamani J

Agrawal S

References (21)

21 references, click to expand

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Article Info

Journal

Nucleic acids research

Abbr.

Nucleic Acids Res

ISSN

0305-1048

DOI

10.1093/nar/21.11.2729

Published

1993-06-11

Pages

2729-35

Language

English

Region

England

NLM ID

0411011

PMCID

PMC309610

Subset

External Links

PubMed source DOI: 10.1093/nar/21.11.2729 PMC Full Text View journal details

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Self-stabilized antisense oligodeoxynucleotide phosphorothioates: properties and anti-HIV activity.

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