Anti-HIV peptides
Simple β-hairpin peptides in linear and cyclic form that specifically bind to HIV-1 Trans-Activation Response element (HIV-1 TAR), as well as compositions and use thereof are described.
1. An isolated peptide comprising an amino acid sequence, the amino acid sequence consisting of the amino acid sequence of SEQ ID NO: 2, wherein the isolated peptide specifically binds to HIV-1 trans-activation responsive element.
2. The isolated peptide of claim 1 , the amino acid sequence consisting of the amino acid sequence of SEQ ID NO: 3.
3. The isolated peptide of claim 2 , the amino acid sequence consisting of the amino acid sequence of SEQ ID NO: 4.
4. The isolated peptide of claim 1 , the amino acid sequence consisting of 13 amino acid residues at position 4 to position 16 of the amino acid sequence selected from the group consisting of SEQ ID NOs: 8-9 and SEQ ID NOs: 12-22.
5. The isolated peptide of claim 1 , wherein the peptide is a cyclic peptide.
6. The cyclic peptide of claim 5 , wherein the cyclic peptide is a head-to-tail cyclization, a side chain-to-side chain cyclization, a head-to-side chain cyclization, or a side chain-to-tail cyclization.
7. The cyclic peptide of claim 5 , wherein the cyclic peptide is a side chain-to-side chain cyclization and the side chains of the amino acids at positions 1 and 13 are conjugated to form the cyclic peptide.
8. The cyclic peptide of claim 7 , wherein the amino acids at positions 1 and 13 are cysteines.
9. An isolated peptide comprising an amino acid sequence, the amino acid sequence consisting of the amino acid sequence selected from the group consisting of SEQ ID NOs: 5-24 wherein the isolated peptide specifically binds to HIV-1 trans-activation responsive element.
10. The isolated peptide of claim 9 consisting of the amino acid sequence of SEQ ID NO: 6.
11. The isolated peptide of claim 10 consisting of the amino acid sequence of SEQ ID NO: 7.
12. The isolated peptide of claim 9 consisting of the amino acid sequence selected from the group consisting of SEQ ID NOs: 8-24.
13. The isolated peptide of claim 9 , wherein the peptide is a cyclic peptide.
14. The cyclic peptide of claim 13 , wherein the cyclic peptide is a head-to-tail cyclization, a side chain-to- side chain cyclization, a head-to-side chain cyclization, or a side chain-to-tail cyclization.
15. The cyclic peptide of claim 13 , wherein the cyclic peptide is a side chain-to-side chain cyclization and the side chains of the amino acids at positions 2 and 18, or the amino acids at positions 4 and 16, are conjugated to form the cyclic peptide.
16. The cyclic peptide of claim 15 , wherein the amino acids at positions 2 and 18 of SEQ ID NO: 5, or the amino acids at positions 4 and 16 of SEQ ID NO: 5, are cysteines.
17. A cyclic peptide comprising an amino acid sequence, the amino acid sequence comprising the 13 amino acid residues at position 4 to position 16 of one of SEQ ID NOs: 7-24.
18. The cyclic peptide of claim 17 , wherein the 13 amino acid sequence comprises residues at position 4 to position 16 of SEQ ID NO: 15.
19. The cyclic peptide of claim 17 , wherein the 13 amino acid sequence comprises residues at position 4 to position 16 of one of SEQ ID NOs: 8-24.
20. The cyclic peptide of claim 17 , wherein the cyclic peptide specifically binds to HIV-1 trans-activation responsive element.
21. The cyclic peptide of claim 17 , wherein the cyclic peptide is a head-to-tail cyclization, a side chain-to-side chain cyclization, a head-to-side chain cyclization, or a side chain-to-tail cyclization.
22. The cyclic peptide of claim 17 , wherein the cyclic peptide is a side chain-to-side chain cyclization and the side chains of the amino acids at positions 4 and 16 of SEQ ID NO: 7-24 are conjugated to form the cyclic peptide.
23. The cyclic peptide of claim 22 , wherein the amino acids at positions 4 and 16 of SEQ ID NO: 7 are cysteines.
24. A cyclic peptide comprising an amino acid sequence, the amino acid sequence comprising the amino acid sequence of one or SEQ ID NOs: 5-24.
25. The cyclic peptide of claim 24 comprising the amino acid sequence of SEQ ID NO: 6.
26. The cyclic peptide of claim 25 comprising the amino acid sequence of SEQ ID NO: 7.
27. The cyclic peptide of claim 24 , wherein the amino acid sequence is one of SEQ ID NOs: 8-24.
28. The cyclic peptide of claim 24 , wherein the cyclic peptide specifically binds to HIV-1 trans-activation responsive element.
29. The cyclic peptide of claim 24 , wherein the cyclic peptide is a head-to-tail cyclization, a side chain-to-side chain cyclization, a head-to-side chain cyclization, or a side chain-to-tail cyclization.
30. The cyclic peptide of claim 24 , wherein the cyclic peptide is a side chain-to-side chain cyclization and the side chains of the amino acids at positions 2 and 18 of SEQ ID NO: 5, or the amino acids at positions 4 and 16 of SEQ ID NO: 5, are conjugated to form the cyclic peptide.
31. The cyclic peptide of claim 30 , wherein the amino acids at positions 2 and 18, or the amino acids at positions 4 and 16, are cysteines.
32. A pharmaceutical composition comprising the peptide of claim 1 .
33. A method of inhibiting the interaction between HIV Tat and HIV TAR, the method comprising contacting an HIV infected cell with the peptide of claim 1 .
34. A method of reducing HIV proliferation, the method comprising contacting an HIV infected cell with the peptide of claim 1 .