Peptide derivative fusion inhibitors of hiv infection

Abstract

This invention relates to gp41 peptide derivatives that are inhibitors of viral infection and/or exhibit antifusogenic properties. In particular, this invention relates to gp41 derivatives having inhibiting activity against human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) with enhanced duration of action for the treatment of the respective viral infections.

1 - 36 . (canceled) 
     
     
         37 . An isolated, modified peptide comprising the amino acid sequence of SEQ ID NO:1; SEQ ID NO:2, SEQ ID NO:3 or SEQ ID NO:7, and having at least one substituted amino acid residue at a predetermined position in the peptide sequence, wherein the at least one substituted amino acid residue is a hydrophilic amino acid residue, a hydrophobic amino acid residue, an amino acid residue having a propensity to form alpha helices, a D-isomer of one of the naturally occurring L-amino acids, or a non-naturally occurring amino acid residue. 
     
     
         38 . An isolated peptide derivatized with a maleimide linking moiety comprising the amino acid sequence of SEQ ID NO:3; SEQ ID NO:12, or SEQ ID NO:13. 
     
     
         39 . The derivatized peptide of  claim 38 , wherein the maleimido group is 3′-maleimidopropionate connected to the epsilon amino group of lysine by [2-(2-amino)ethoxyl]ethoxy acetic acid. 
     
     
         40 . A pharmaceutical composition comprising the peptide of  claim 37 . 
     
     
         41 . A pharmaceutical composition comprising the derivatized peptide of  claim 38 . 
     
     
         42 . A conjugate comprising the derivatized peptide of  claim 37  conjugated to a blood component. 
     
     
         43 . The conjugate of  claim 42 , wherein the blood component is human serum albumin protein, human transferrin protein, human ferritin protein, human immunoglobulin proteins, human ferritin protein, human α-2-macroglobulin protein, human thyroxin binding protein, human steroid binding proteins, or a combination thereof. 
     
     
         44 . A conjugate comprising the derivatized peptide of  claim 38  conjugated to a blood component. 
     
     
         45 . The conjugate of  claim 44 , wherein the blood component is human serum albumin protein, human transferrin protein, human ferritin protein, human immunoglobulin proteins, human ferritin protein, human α-2-macroglobulin protein, human thyroxin binding protein, human steroid binding proteins, or a combination thereof. 
     
     
         46 . A method of inhibiting HIV-1 viral replication in a host comprising administrating the peptide of  claim 37 . 
     
     
         47 . The method of  claim 46 , wherein the peptide is administered orally, topically, intravascularly, intraarterially, intramuscularly, or subcutaneously. 
     
     
         48 . The method of  claim 46 , wherein the peptide is co-administered with one or more additional HIV treatment(s). 
     
     
         49 . The method of  claim 46 , wherein the said one or more additional HIV treatment(s) comprises at least one other variant gp41 peptide. 
     
     
         50 . The method of  claim 49 , wherein the additional HIV treatment(s) is selected from the group consisting of: AGENERASE, COMBIVIR, CRIXIVAN, EMTRIVA, EPIVIR, FORTOVASE, HIVID, INVIRASE, KALETRA, NORVIR, RESCRIPTOR, RETROVIR, REYATAZ, SUSTIVA, TRIZIVIR, VIDEX EC, VIDEX, VIRACEPT, VIRAMUNE, VIREAD, ZERIT, ZIAGEN, or combinations thereof. 
     
     
         51 . A method of inhibiting HIV-1 viral replication in a host comprising administrating the derivatized peptide of  claim 38 . 
     
     
         52 . The method of  claim 51 , wherein the derivatized peptide is administered orally, topically, intravascularly, intraarterially, intramuscularly, or subcutaneously. 
     
     
         53 . The method of  claim 52 , wherein the derivatized peptide is co-administered with one or more additional HIV treatment(s). 
     
     
         54 . The method of  claim 53 , wherein the said one or more additional HIV treatment(s) comprises at least one other variant gp41 peptide. 
     
     
         55 . The method of  claim 54 , wherein the additional HIV treatment(s) is selected from the group consisting of: AGENERASE, COMBIVIR, CRIXIVAN, EMTRIVA, EPIVIR, FORTOVASE, HIVID, INVIRASE, KALETRA, NORVIR, RESCRIPTOR, RETROVIR, REYATAZ, SUSTIVA, TRIZIVIR, VIDEX EC, VIDEX, VIRACEPT, VIRAMUNE, VIREAD, ZERIT, ZIAGEN, or combinations thereof.