Modification of polypeptides

Abstract

The invention provides a method for conjugating a peptide displayed on a genetic display system to a molecular scaffold performed on an ion exchange resin.

What is claimed is: 
     
         1 . A method for conjugating a peptide displayed on a genetic display system to a molecular scaffold, comprising the steps of:
 (a) combining polypeptides displayed on a genetic display system with a purification resin such that the display system is bound to the resin and treating the bound display system with a reducing agent;   (b) exposing the bound display system to the molecular scaffold;   (c) removing unreacted molecular scaffold from the bound display system; and   (d) eluting the display system from the purification resin.   
     
     
         2 . The method according to  claim 1 , wherein the display system is phage display. 
     
     
         3 . The method according to  claim 1 , wherein step (a) is followed by a washing step before addition of the molecular scaffold 
     
     
         4 . The method according to  claim 3 , wherein the display system is washed in a dilute solution of reducing agent. 
     
     
         5 . The method according to  claim 4 , wherein the wash solution further comprises a chelating agent. 
     
     
         6 . The method according to  claim 1 , wherein the reducing agent is TCEP. 
     
     
         7 . The method according to  claim 1 , wherein the scaffold is TBMB. 
     
     
         8 . The method according to  claim 1 , wherein the molecular scaffold is added in the presence of aqueous acetonitrile. 
     
     
         9 . The method according to  claim 1 , wherein the resin is an anion exchange resin. 
     
     
         10 . The method according to  claim 1 , wherein the resin is magnetic. 
     
     
         11 . The method according to  claim 1 , wherein step (a) is performed for 20 minutes at room temperature. 
     
     
         12 . The method according to  claim 1 , wherein step (b) is performed for 10 minutes at room temperature.