Fusion proteins comprising dp-178 and other viral fusion inhibitor peptides useful for treating aids

Abstract

The present invention relates to fusion peptides which exhibit potent anti-retroviral activity. The fusion peptides of the invention comprise a macromolecular carrier group fused to a gp41-derived DP178 (SEQ ID NO:1) peptide corresponding to amino acids 638 to 673 of the HIV-1 LAI gp41 protein, or fragments, analogs or homologs of DP178. The invention further relates to the uses of such fusion peptides as inhibitory of human and non-human retroviral, especially HIV, transmission to uninfected cells.

1 - 39 . (canceled) 
     
     
         40 . A fusion protein comprising a macromolecular carrier group fused to a gp41-derived peptide, wherein:
 (a) the macromolecular carrier group comprises a peptide group; and   (b) the gp41-derived peptide has an amino acid sequence (i) corresponding to a region of gp41 from which SEQ ID NO. 1 was derived, and (ii) being other than SEQ ID NO. 1, wherein such peptide is derived from a strain of HIV other than HIV-1 LAI ; and   wherein the fusion protein exhibits anti-HIV activity.   
     
     
         41 . A fusion protein comprising a macromolecular carrier group fused to a gp41-derived peptide, wherein:
 (a) the macromolecular carrier group comprises a peptide group;   (b) the gp41-derived peptide has an amino acid sequence (i) corresponding to a region of gp41 from which SEQ ID NO. 210 was derived, and (ii) having from 1 to 22 contiguous amino acids truncated from its amino terminus, wherein such peptide is derived from a strain of HIV other than HIV-1 LAI ; and   wherein the fusion protein exhibits anti-HIV activity.   
     
     
         42 . A fusion protein comprising a macromolecular carrier group fused to a gp41-derived peptide, wherein:
 (a) the macromolecular carrier group comprises a peptide group;   (b) the gp41-derived peptide has an amino acid sequence (i) corresponding to a region of gp41 from which SEQ ID NO. 210 was derived, (ii) having from 1 to 22 contiguous amino acids truncated from its carboxy terminus, and (iii) being other than T661 (SEQ ID NO. 893), wherein such peptide is derived from a strain of HIV other than HIV-1 LAI ; and   wherein the fusion protein exhibits anti-HIV activity.   
     
     
         43 . A fusion protein comprising a macromolecular carrier group fused to a gp41-derived peptide, wherein:
 (a) the macromolecular carrier group comprises a peptide group;   (b) the gp41-derived peptide has an amino acid sequence (i) corresponding to a region of gp41 from which SEQ ID NO. 210 was derived, (ii) having from 1 to 22 contiguous amino acids truncated from its amino terminus and from 1 to 22 contiguous amino acids truncated from its carboxy terminus, and (iii) being other than T661 (SEQ ID NO. 893); T660 (SEQ ID NO. 894); T659 (SEQ ID NO. 895); T658 (SEQ ID NO. 896); T657 (SEQ ID NO. 897); T656 (SEQ ID NO. 898); T655 (SEQ ID NO. 899); T654 (SEQ ID NO. 900); T653 (SEQ ID NO. 901); T652 (SEQ ID NO. 902); T651 (SEQ ID NO. 903); T625 (SEQ ID NO. 904); T650 (SEQ ID NO. 905); T649 (SEQ ID NO. 906); T624 (SEQ ID NO. 907); T50 (SEQ ID NO. 908); T648 (SEQ ID NO. 909); T647 (SEQ ID NO. 910); T711 (SEQ ID NO. 911); T621 (SEQ ID NO. 912); T646 (SEQ ID NO. 913); T645 (SEQ ID NO. 914); T644 (SEQ ID NO. 915); T643 (SEQ ID NO. 916); T642 (SEQ ID NO. 917); T622 (SEQ ID NO. 918); T623 (SEQ ID NO. 919); T51 (SEQ ID NO. 920), T641 (SEQ ID NO. 921); T640 (SEQ ID NO. 922); or T20 (SEQ ID NO. 1), wherein such peptide is derived from a strain of HIV other than HIV-1 LAI ; and   wherein the fusion protein exhibits anti-HIV activity.   
     
     
         44 . A fusion protein comprising a macromolecular carrier group fused to a gp41-derived peptide, wherein:
 (a) the macromolecular carrier group comprises a peptide group;   (b) the gp41-derived peptide has an amino acid sequence (i) corresponding to a region of gp41 from which SEQ ID NO. 160 was derived, and (ii) having from 1 to 7 contiguous amino acids truncated from its amino terminus, wherein such peptide is derived from a strain of HIV other than HIV-1 LAI ; and   wherein the fusion protein exhibits anti-HIV activity.   
     
     
         45 . A fusion protein comprising a macromolecular carrier group fused to a gp41-derived peptide, wherein:
 (a) the macromolecular carrier group comprises a peptide group;   (b) the gp41-derived peptide has an amino acid sequence (i) corresponding to a region of gp41 from which SEQ ID NO. 160 was derived, (ii) having from 1 to 13 contiguous amino acids truncated from its carboxy terminus, and (iii) being other than T20 (SEQ ID NO. 1), wherein such peptide is derived from a strain of HIV other than HIV-1 LAI ; and   wherein the fusion protein exhibits anti-HIV activity.   
     
     
         46 . A fusion protein comprising a macromolecular carrier group fused to a gp41-derived peptide, wherein:
 (a) the macromolecular carrier group comprises a peptide group;   (b) the gp41-derived peptide has an amino acid sequence (i) corresponding to a region of gp41 from which SEQ ID NO. 160 was derived, (ii) having from 1 to 7 contiguous amino acids truncated from its amino terminus and from 1 to 13 contiguous amino acids truncated from its carboxy terminus, and (iii) being other than T20 (SEQ ID NO. 1); T639 (SEQ ID NO. 925); T638 (SEQ ID NO. 926); T637 (SEQ ID NO. 927); T636 (SEQ ID NO. 928); T635 (SEQ ID NO. 929); T634 (SEQ ID NO. 930); or T633 (SEQ ID NO. 931), wherein such peptide is derived from a strain of HIV other than HIV-1 LAI ; and   wherein the fusion protein exhibits anti-HIV activity.   
     
     
         47 . The fusion protein of any one of  claims 40 - 46 , wherein the peptide group comprises a polypeptide. 
     
     
         48 . A recombinant vector comprising a nucleic acid molecule encoding the fusion protein of any one of  claims 40 - 46 . 
     
     
         49 . A recombinant vector comprising a nucleic acid molecule encoding the fusion protein of  claim 47 .