METHODS FOR IDENTIFYING AND USING MarR FAMILY POLYPEPTIDE BINDING COMPOUNDS

Abstract

Methods for identifying MarR family inhibiting compounds are described. The methods include the use of computer aided rational based drug design programs and three dimensional structures of MarR family polypeptides.

1 - 21 . (canceled) 
     
     
         22 . A MarR modulating compound of the formula(I):
   X-Y-Z   (I)
   wherein
 X is an interacting moiety; 
 Y is a hydrophobic moiety; and 
 Z is a polar moiety. 
   
     
     
         23 . The MarR modulating compound of  claim 22 , wherein said interacting moiety interacts with the amino acid Thr at position 72 of SEQ ID. 1. 
     
     
         24 . The MarR modulating compound of  claim 22 , wherein said interacting moiety interacts with the amino acid Ala at position 70 of SEQ ID No. 1. 
     
     
         25 . The MarR modulating compound of  claim 24 , wherein said interacting moiety is capable of hydrogen bonding. 
     
     
         26 . The MarR modulating compound of  claim 25 , wherein said interacting moiety is selected from the group consisting of hydroxyl, thiol, sulfonyl, amino, carbonyl, alkyl, and acyl moieties. 
     
     
         27 . The MarR modulating compound of  claim 26 , wherein said interacting moiety is hydroxy, thiol, or amino. 
     
     
         28 . The MarR modulating compound of  claim 27 , wherein said hydrophobic moiety is selected from the group consisting of substituted and unsubstituted alkyl, alkenyl, alkynyl, and aryl moieties. 
     
     
         29 . The MarR modulating compound of  claim 28 , wherein said hydrophobic moiety is aryl. 
     
     
         30 . The MarR modulating compound of  claim 22 , wherein said hydrophobic moiety is capable of interacting hydrophobically with the amino acid Pro at position 57 or the amino acid Met at position 74 of MarR. 
     
     
         31 . The MarR modulating compound of  claim 22 , wherein said polar moiety is capable of interacting with the amino acid Arg at position 86 of MarR. 
     
     
         32 . The MarR modulating compound of  claim 22 , wherein said polar moiety is capable of interacting with the amino acid Arg at position 77 of MarR. 
     
     
         33 . The MarR modulating compound of  claim 22 , wherein said polar moiety is negatively charged. 
     
     
         34 . The MarR modulating compound of  claim 22 , wherein said polar moiety is selected from the group consisting of: carboxylate, phosphate, phosphite, sulfate, sulfite, nitrate, nitrite, nitro, hydroxy, oxalate, and perchlororate. 
     
     
         35 . The MarR modulating compound of  claim 34 , wherein said polar moiety is carboxylate. 
     
     
         36 . The MarR modulating compound of  claim 22 , wherein said MarR modulating compound is a MarR inhibitor. 
     
     
         37 . The MarR modulating compound of  claim 22 , wherein said MarR modulating compound is of the formula: 
       
         
           
           
               
               
           
         
         wherein 
         Y is a substituted or unsubstituted cyclic or bicyclic moiety, and pharmaceutically acceptable salts and esters thereof. 
       
     
     
         38 . The method of  claim 37 , wherein X is hydroxyl. 
     
     
         39 . The method of  claim 37 , wherein Y is monocyclic. 
     
     
         40 . The method of  claim 37 , wherein Y is bicyclic. 
     
     
         41 . The method of  claim 37 , wherein said MarR modulating compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         42 - 47 . (canceled)