Protein synthesis modulators

Abstract

The invention provides a high resolution three-dimensional structure of cycloheximide, either alone or in association with a large ribosomal subunit. The invention provides methods for designing and/or identifying cycloheximide analogs and derivatives that bind and/or modulate the protein biosynthetic activity of the ribosome.

1 .- 18 . (canceled) 
     
     
         19 . A method of identifying a candidate molecule, the method comprising the steps of:
 (a) providing a molecular model of at least a portion of a cycloheximide molecule bound to a cycloheximide binding site of a large subunit of a ribosome; and   (b) using the molecular model to identify a candidate molecule capable of binding to the cycloheximide binding site; and   (c) producing the candidate molecule identified in step (b).   
     
     
         20 . The method of  claim 19 , wherein the candidate molecule is capable of interacting stereochemically with the binding site. 
     
     
         21 . The method of  claim 19 , wherein the candidate molecule is capable of binding specifically to the binding site. 
     
     
         22 . The method of  claim 19  comprising the additional step of determining whether the candidate molecule modulates ribosomal activity. 
     
     
         23 . The method of  claim 22  comprising the additional step of modifying the candidate molecule. 
     
     
         24 . The method of  claim 23  comprising the additional step of producing the modified candidate molecule. 
     
     
         25 . The method of  claim 24  comprising the additional step of determining whether the candidate molecule modulates ribosomal activity. 
     
     
         26 . The method of  claim 25  comprising the additional step of producing the candidate molecule. 
     
     
         27 . The method of  claim 19 , wherein the molecular model is defined by at least a portion of the atomic co-ordinates recorded on Disk No. 1 under file name cycloheximide.pdb. 
     
     
         28 .- 41 . (canceled)