Nucleic acids encoding DP-178 and other viral fusion inhibitor peptides useful for treating aids
The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention comprise DP178 (SEQ ID:1) peptide corresponding to amino acids 638 to 673 of the HIV-1 LAI gp41 protein, and fragments, analogs and homologs of DP178. The invention further relates to the uses of such peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.
1. An isolated nucleic acid molecule encoding a peptide consisting of the amino acid sequence of DP-178 (SEQ ID NO:1).
2. An isolated nucleic acid molecule encoding a peptide consisting of the amino acid sequence of
X-YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF-Z (SEQ ID NO:1),
wherein the peptide amino acid residues are presented by the single-letter code, further wherein:
X comprises an amino group, an acetyl group, a 9-fluorenylmethoxy-carbonyl group, a hydrophobic group, or a macromolecule carrier group; and
Z comprises a carboxyl group, an amido group, a hydrophobic group, or a macromolecular carrier group.
3. The nucleic acid of claim 2 , wherein X is a hydrophobic group.
4. The nucleic acid of claim 3 , wherein the hydrophobic group X is carbobenzoxyl, dansyl, or t-butyloxycarbonyl.
5. The nucleic acid of claim 2 , wherein Z is a hydrophobic group.
6. The nucleic acid of claim 5 , wherein the hydrophobic group Z is t-butyloxycarbonyl.
7. The nucleic acid of claim 2 , wherein X is a macromolecular carrier group.
8. The nucleic acid of claim 7 , wherein the macromolecular carrier group is a lipid-fatty acid conjugate, a polyethylene glycol, or a carbohydrate moiety.
9. The nucleic acid of claim 2 , wherein Z is a macromolecular carrier group.
10. The nucleic acid of claim 9 , wherein the macromolecular carrier group Z is a lipid-fatty acid conjugate, a polyethylene glycol, or a carbohydrate moiety.
11. The nucleic acid of claim 2 , wherein at least one bond linking adjacent amino acid residues is a non-peptide bond.
12. The nucleic acid of claim 11 , wherein the non-peptide bond is an imino, ester, hydrazine, semicarbazide, or azo bond.
13. The nucleic acid of claim 2 , wherein at least one amino acid residue is in a D-isomer configuration.
14. The nucleic acid of claim 2 , wherein the peptide comprises between one and three amino acid substitutions of a first amino acid residue for a second, different amino acid residue.
15. A recombinant vector comprising the nucleic acid molecule of claim 1 .
16. A recombinant vector comprising a nucleic acid molecule encoding a fusion protein comprising DP-178 (SEQ ID NO:1).