Combinatorially selected guanosine-quartet structure is a potent inhibitor of human immunodeficiency virus envelope-mediated cell fusion

J R Wyatt; T A Vickers; J L Roberson; R W Buckheit Jr; T Klimkait; E DeBaets; P W Davis; B Rayner; J L Imbach; D J Ecker

doi:10.1073/pnas.91.4.1356

Combinatorially selected guanosine-quartet structure is a potent inhibitor of human immunodeficiency virus envelope-mediated cell fusion

Proc Natl Acad Sci U S A. 1994 Feb 15;91(4):1356-60. doi: 10.1073/pnas.91.4.1356.

Authors

J R Wyatt¹, T A Vickers, J L Roberson, R W Buckheit Jr, T Klimkait, E DeBaets, P W Davis, B Rayner, J L Imbach, D J Ecker

Affiliation

¹ ISIS Pharmaceuticals, Carlsbad, CA 92008.

Abstract

The phosphorothioate oligonucleotide T2G4T2 was identified as an inhibitor of HIV infection in vitro by combinatorial screening of a library of phosphorothioate oligonucleotides that contained all possible octanucleotide sequences. The oligonucleotide forms a parallel-stranded tetrameric guanosine-quartet structure. Tetramer formation and the phosphorothioate backbone are essential for antiviral activity. The tetramer binds to the human immunodeficiency virus envelope protein gp120 at the V3 loop and inhibits both cell-to-cell and virus-to-cell infection.

MeSH terms

Antiviral Agents / pharmacology*
CD4-Positive T-Lymphocytes / metabolism
CD4-Positive T-Lymphocytes / microbiology
Cell Fusion / drug effects*
Cells, Cultured
Dose-Response Relationship, Drug
HIV Envelope Protein gp120 / metabolism*
HIV-1 / drug effects*
HIV-1 / growth & development
HIV-1 / pathogenicity
Humans
Oligodeoxyribonucleotides / chemical synthesis
Oligodeoxyribonucleotides / metabolism
Oligodeoxyribonucleotides / pharmacology*
Thionucleotides / chemical synthesis
Thionucleotides / metabolism
Thionucleotides / pharmacology*
Virulence / drug effects

Substances

Antiviral Agents
HIV Envelope Protein gp120
Oligodeoxyribonucleotides
Thionucleotides
oligonucleotide 5320