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|Title:||Ligands of HIV-1 tat protein|
|Abstract:||Methods are described for the production of nucleic acid ligands to the HIV-1 tat protein. Motifs I, II and III in FIG. 3 are nucleic acid ligands identified by the disclosed methods.|
|Inventor(s):||Gold; Larry M. (Boulder, CO), Tuerk; Craig (Boulder, CO)|
|Assignee:||NeXstar Pharmacueticals, Inc. (Boulder, CO)|
|Filing Date:||May 17, 1994|
|Claims:||1. A nucleic acid ligand to the HIV-1 tat protein produced according to a method comprising: |
a) preparing a candidate mixture of nucleic acids;
b) contacting the candidate mixture with the HIV-1 tat protein, wherein nucleic acids having an increased affinity to the HIV-1 tat protein relative to the candidate mixture may be partitioned from the remainder of the candidate mixture;
c) partitioning the increased affinity nucleic acids from the remainder of the candidate mixture; and
d) amplifying the increased affinity nucleic acids to yield a mixture of nucleic acids enriched for nucleic acids an increased affinity to the protein; whereby nucleic acid ligands of the HIV-1 tat protein are produced.
2. The nucleic acid ligand of claim 1 being a single stranded nucleic acid.
3. The nucleic acid ligand of claim 1 being a single stranded RNA.
4. A purified and isolated non-naturally occurring nucleic acid ligand to the HIV-1 tat protein.
5. The nucleic acid ligand of claim 4 wherein said ligand is selected from the group consisting of the sequences set forth in FIG. 2.
6. The nucleic acid ligand of claim 4 wherein said ligand is selected from the group consisting of: motif I (SEQ ID NOS.:4-10), motif II (SEQ ID NOS.:11-15), and motif III (SEQ ID NOS.:16-17), as shown in FIG. 3, wherein X is a non-conserved nucleotide position, X' is a base-pairing complement to X at that position in a helix, R is a purine and Y is a pyrimidine.
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