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|Title:||Synthetic peptide inhibitors of HIV transmission|
|Abstract:||The present invention relates to peptides which exhibit potent anti-retroviral activity. The peptides of the invention comprise DP-178 (SEQ ID:1) ptides corresponding to amino acids 638 to 673 of the HIV-1.sub.LAI gp41 protein, and fragments, analogs and homologs of DP-178. The invention further relates to the uses of such peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.|
|Inventor(s):||Bolognesi; Dani P. (Durham, NC), Matthews; Thomas J. (Durham, NC), Wild; Carl T. (Durham, NC)|
|Assignee:||Duke University (Durham, NC)|
1. A peptide having a formula selected from the group consisting of:
X-YTSLIHSLIEESQNQQEKNEQELLELDKWASLWNWF-Z ( SEQ ID: 1)
X-YTNTIYTLLEESQNQQEKNEQELLELDKWASLWNWF-Z (SEQ ID NO:3)
X-YTGIIYNLLEESQNQQEKNEQELLELDKWANLWNWF-Z (SEQ ID NO:4)
X-YTSLIYSLLEKSQIQQEKNEQELLELDKWASLWNWF-Z (SEQ ID NO:5)
X-LEANISKSLEQAQIQQEKNMYELQKLNSWDIFGNWF-Z (SEQ ID NO:6)
X-LEANISQSLEQAQIQQEKNMYELQKLNSWDVFTNWL-Z (SEQ ID NO:7),
amino acid residues are presented by the single-letter code;
X comprises an amino group, an acetyl group, a 9-fluorenylmethoxy-carbonyl group, a hydrophobic group, or a macromolecule carrier group;
Z comprises a carboxyl group, an amido group, a hydrophobic group, or a macromolecular carrier group.
2. The peptide of claim 1 wherein X is a hydrophobic group.
3. The peptide of claim 2 wherein the hydrophobic group X is carbobenzoxyl, dansyl, or t-butyloxycarbonyl.
4. The peptide of claim 1 wherein Z is a hydrophobic group.
5. The peptide of claim 4 wherein the hydrophobic group Z is t-butyloxycarbonyl.
6. The peptide of claim 1 wherein X is a macromolecular carrier group.
7. The peptide of claim 6 wherein the macromolecular carrier group is a lipid-fatty acid conjugate, a polyethylene glycol, or a carbohydrate moiety.
8. The peptide of claim 1 wherein Z is a macromolecular carrier group.
9. The peptide of claim 8 wherein the macromolecular carrier group Z is a lipid-fatty acid conjugate, a polyethylene glycol, or a carbohydrate moiety.
10. The peptide of claim 1 wherein at least one bond linking adjacent amino acid residues is a non-peptide bond.
11. The peptide of claim 10 wherein the non-peptide bond is an imino, ester, hydrazine, semicarbazide, or azo bond.
12. The peptide of claim 1 wherein at least one amino acid residue is in a D-isomer configuration.
13. The peptide of claim 1 further comprising at least one amino acid substitution wherein a first amino acid residue is substituted for a second, different amino acid residue.
14. The peptide of claim 13 wherein the amino acid substitution is a conserved substitution.
15. The peptide of claim 13 wherein the amino acid substitution is a non-conserved substitution.
16. The peptide homolog of claim 1 wherein the HIV retrovirus is a HIV-1 retrovirus.
17. The peptide homolog of claim 16 wherein the HIV-1 retrovirus is HIV-1.sub.SF2.
18. The peptide homolog of claim 16 wherein the retrovirus is HIV-1.sub.RF.
19. The peptide homolog of claim 16 wherein the retrovirus is HIV-1.sub.MN.
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