Tat-derived oligourea and its method of production and use in high affinity and specific binding HIV-1 TAR RNA
View Patent ↗This invention relates to the use of oligourea molecules to specifically inhibit protein-nucleic acid interactions. In particular, it provides an oligourea molecule that competes with the Tat molecule for the TAR RNA of HIV-1. Also provided is a method specifically inhibiting protein-nucleic and interactions, and kits.
1. A synthesized oligourea comprising the following structure:
wherein n=3–50; and R 1 and R 2 are independently each amino acid side chains comprising the basic-arginine rich region of HIV-1 Tat protein.
2. A method of inhibiting the binding of Tat protein to Tar RNA comprising introducing the oligourea of claim 1 into a cellular environment in vitro wherein the inhibition is sought to occur.
3. The method of claim 2 wherein the cellular environment is one infected by the HIV-1.
4. The method of claim 3 wherein the oligourea of claim 1 binds to the TAR RNA of HIV-1, thereby limiting the binding of Tat to TAR RNA.
5. A composition comprising an oligourea, wherein the oligourea comprises the following structure:
wherein n=3–50; and R 1 and R 2 are independently each amino acid side chains comprising the basic-arginine rich region of HIV-1 Tat protein.
6. The composition of claim 5 , wherein the R 1 and R 2 amino acid side-chains correspond to SEQ ID NO: 1.
7. The composition of claim 5 , wherein the R 1 and R 2 amino acid side-chains correspond to the SEQ ID NO: 1 with a L-Tyr amino acid at the carboxyl-terminus.
8. The oligourea of claim 1 , wherein the R 1 and R 2 amino acid side chains correspond to SEQ ID NO:1.
9. The oligourea of claim 1 , wherein the R 1 and R 2 amino acid side chains correspond to SEQ ID NO:1 with a L-Tyr amino acid at the carboxyl-terminus.
10. The oligourea of claim 1 , wherein the R 1 and R 2 amino acid side chains correspond to SEQ ID NO:1 with a L-Tyr amino acid at the amino-terminus.
11. The oligourea of claim 1 , wherein n is 5–30.
12. The oligourea of claim 1 , wherein n is 8–25.
13. The composition of claim 5 , wherein the R 1 and R 2 amino acid side chains correspond to SEQ ID NO:1 with a L-Tyr amino acid at the amino-terminus.