Peptide inhibitors of protein synthesis

Abstract

The present invention discloses compositions of peptide inhibitors of protein synthesis, and methods of identifying peptide inhibitors that are capable of inhibiting protein synthesis through an interaction at a stem-loop H18 in 16S rRNA of a 30S ribosomal subunit. Screening methods for peptides are disclosed, in addition to methods of determining the affinity of a test compound for a ribosomal subunit.

1 . An isolated therapeutic peptide composition comprising:
 a sequence of at least seven amino acids capable of inhibiting protein synthesis through an interaction at a stem-loop H18 in 16S rRNA of a 30S ribosomal subunit.   
     
     
         2 . The therapeutic peptide composition of  claim 1 , wherein the peptide exhibits at least about 25 percent inhibition of protein synthesis in a cell-free translational assay. 
     
     
         3 . The therapeutic peptide composition of  claim 1 , wherein the peptide exhibits at least about 50 percent inhibition of protein synthesis in a cell-free translational assay. 
     
     
         4 . The therapeutic peptide composition of  claim 1 , wherein the peptide is in the range of about seven to about thirty amino acid residues and selectively binds to the stem-loop H18 in 16S rRNA of the 30S ribosomal subunit. 
     
     
         5 . The therapeutic peptide composition of  claim 1 , wherein the peptide sequence comprises at least one sequence selected from the group consisting of SEQ ID NOS: 2-33. 
     
     
         6 . The therapeutic peptide composition of  claim 1 , wherein the peptide sequence comprises at least one of the amino acid motifs selected from the group consisting of AMS, HPP, THP, LHL, SXPXP (SEQ ID NO: 6) and SXXLPT (SEQ ID NO: 7). 
     
     
         7 . The therapeutic peptide composition of  claim 1 , wherein the peptide sequence comprises at least one sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 3, and SEQ ID NO: 28. 
     
     
         8 . The therapeutic peptide composition of  claim 1 , further comprising a pharmaceutically acceptable carrier. 
     
     
         9 . The therapeutic peptide composition of  claim 1 , wherein the peptide is coupled to a moiety capable of directing the peptide to a target cell. 
     
     
         10 - 24 . (canceled) 
     
     
         25 . A method for treating a bacterial infection in a subject comprising administrating the therapeutic peptide composition of  claim 1 . 
     
     
         26 . (canceled) 
     
     
         27 . (canceled) 
     
     
         28 . The method of  claim 25 , wherein the peptide is delivered in an amount sufficient to inhibit the growth of bacteria in vivo. 
     
     
         29 . The method of  claim 25 , wherein said peptide is delivered locally or regionally to a site of infection. 
     
     
         30 . The method of  claim 25 , wherein said peptide is administered to a wound site. 
     
     
         31 . The method of  claim 25 , wherein said peptide is administered topically. 
     
     
         32 . The method of  claim 25 , wherein said peptide is delivered systemically. 
     
     
         33 . The method of  claim 25 , wherein said peptide is delivered via intravenous or intra-arterial injection. 
     
     
         34 . The method of  claim 25 , further comprising administering to said subject one or more antimicrobial compounds. 
     
     
         35 . A method for preventing a microbial infection in a subject comprising administrating the therapeutic peptide composition of  claim 1  in an amount sufficient to inhibit the growth of microbes in vivo. 
     
     
         36 . A method for preventing microbial growth in a solution comprising mixing said solution with the therapeutic peptide composition of  claim 1  in an amount sufficient to inhibit the microbial growth in said solution. 
     
     
         37 . A method for preventing bacterial attachment or growth on an abiotic surface comprising coating said surface with the therapeutic peptide composition of  claim 1  in an amount sufficient to inhibit the growth of bacteria on said abiotic surface. 
     
     
         38 . The method of  claim 37 , wherein said surface is part of a medical device. 
     
     
         39 . The method of  claim 37 , wherein said medical device is a syringe, a stent, a catheter, fluid container, a pacemaker, or an implantable pump. 
     
     
         40 .- 48 . (canceled)