Small molecule composite surfaces as inhibitors of protein-protein interactions

Abstract

A method of inhibiting a binding event between a target protein and a binding protein, comprising administering to a cell in vitro an effective amount of a non-naturally occurring bifunctional inhibitor molecule including (a) protein binding moiety, and (b) an effector region, wherein the protein binding moiety binds to a blocking protein, and wherein the effector region binds to the target protein in order to bind the target protein and the blocking protein and prevent access of the binding protein to the target protein. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

What is claimed is: 
     
         1 . A compound comprising (a) a protein binding moiety and (b) an effector region, wherein said protein binding moiety binds to a blocking protein, and wherein said effector region binds to a target protein, and further wherein the protein binding moiety is: 
       
         
           
           
               
               
           
         
         wherein R I-  is D(3-homoPhe; R 2  is D-Ala; R 3  is L-Ala; R 4  is L-Ala; R 5  is L-Ala; and R 6  is hydrogen or L-Ala. 
       
     
     
         2 . The compound of  claim 1 , wherein R 6  is L-Ala. 
     
     
         3 . A method of inhibiting a binding event between a target protein and a binding protein, comprising:
 administering to a cell in vitro an effective amount of the compound of claim  21 .   
     
     
         4 . The method of  claim 3 , wherein said blocking protein is FKBP. 
     
     
         5 . The method of  claim 3 , wherein the molecule is a cyclic molecule. 
     
     
         6 . The method of  claim 3 , wherein the target protein is K-Ras. 
     
     
         7 . A method of inhibiting a binding event between a target protein and a binding protein, comprising:
 administering to a cell in vitro an effective amount of the compound of claim  22 .   
     
     
         8 . The method of  claim 7 , wherein said blocking protein is FKBP. 
     
     
         9 . The method of  claim 7 , wherein the molecule is a cyclic molecule. 106921-0512 
     
     
         10 . The method of  claim 7 , wherein the target protein is K-Ras. 
     
     
         11 . A method of preparing the compound of  claim 1 , the method comprising the step of covalently bonding the protein binding moiety to the effector region. 
     
     
         12 . The method of  claim 1 , wherein the effector region is generated randomly prior to the bonding step. 
     
     
         13 . A method of preparing the compound of  claim 2 , the method comprising the step of covalently bonding the protein binding moiety to the effector region. 
     
     
         14 . The method of  claim 3 , wherein the effector region is generated randomly prior to the bonding step. 
     
     
         15 . A method of treating a patient having a disorder comprising the step of administering the compound in an amount effective to treat the disorder in the patient, wherein the compound comprises (a) a protein binding moiety and (b) an effector region, wherein said protein binding moiety binds to a blocking protein, and wherein said effector region binds to a target protein, and further wherein the protein binding moiety is: 
       
         
           
           
               
               
           
         
         wherein R I-  is D-β-homoPhe; R 2  is D-Ala; R 3  is L-Ala; R 4  is L-Ala; R 5  is L-Ala; and R 6  is hydrogen or L-Ala. 
       
     
     
         16 . The method of  claim 15 , wherein R 6  is L-Ala. 
     
     
         17 . The method of  claim 15 , wherein the disorder is cancer. 106921-0512 
     
     
         18 . The method of  claim 16 , wherein the disorder is cancer. 
     
     
         19 . A library comprising a multiplicity of bifunctional inhibitor molecules, each of said molecules comprising (a) a protein binding moiety and (b) an effector region, wherein said protein binding moiety binds to a blocking protein, and wherein said effector region binds to a target protein, and further wherein the protein binding moiety is: 
       
         
           
           
               
               
           
         
         wherein R I-  is D-β-homoPhe; R 2  is D-Ala; R 3  is L-Ala; R 4  is L-Ala; R 5  is L-Ala; and R 6  is hydrogen or L-Ala. 
       
     
     
         20 . The library of  claim 19 , wherein R 6  is L-Ala.