RNA pseudoknots that inhibit human immunodeficiency virus type 1 reverse transcriptase.
High-affinity ligands of the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1) were isolated by the SELEX procedure (systematic evolution of ligands by exponential enrichment) from RNA populations randomized at 32 positions. Analysis of these ligands revealed a pseudoknot consensus with primary sequence bias at some positions. We demonstrated that at least one of the ligands inhibits cDNA synthesis by HIV reverse transcriptase but fails to inhibit other reverse transcriptases. These experiments highlight the power of SELEX to yield highly specific ligands that reduce the activity of target proteins. Such ligands may provide therapeutic reagents for viral and other diseases.
Tuerk
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C
Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder 80309.
MacDougal
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S
Gold
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L
D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D015195:Drug Design; D054303:HIV Reverse Transcriptase; D015497:HIV-1 / Q000201:enzymology; D008024:Ligands; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D016372:RNA, Antisense / Q000378:metabolism / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors
D000998:Antiviral Agents; D008024:Ligands; D016372:RNA, Antisense; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase