Solid phase peptide synthesis

Abstract

An improved method of deprotection in solid phase peptide synthesis is disclosed. In particular the deprotecting composition is added in high concentration and small volume to the mixture of the coupling solution, the growing peptide chain, and any excess activated acid from the preceding coupling cycle, and without any draining step between the coupling step of the previous cycle and the addition of the deprotection composition for the successive cycle. Thereafter, the ambient pressure in the vessel is reduced with a vacuum pull to remove the deprotecting composition without any draining step and without otherwise adversely affecting the remaining materials in the vessel or causing problems in subsequent steps in the SPPS cycle.

1 . A system for microwave assisted solid phase peptide synthesis comprising:
 a microwave source positioned to direct microwave radiation into a microwave cavity;   a microwave transparent reaction vessel in said cavity; and   a vacuum source connected to said reaction vessel.   
     
     
         2 . A method according to  claim 1  further comprising a trap between said reaction vessel and said vacuum Source. 
     
     
         3 . A method according to  claim 1  wherein said cavity can support a single mode of microwave radiation at the microwave frequencies produced by said microwave source. 
     
     
         4 . A method according to  claim 3  where wherein said reaction vessel comprises:
 a (glass) frit for draining liquids from said reaction vessel; and 
 a spray head for delivery of reagents to said reaction vessel. 
 
     
     
         5 . A system according to  claim 1  further comprising a fiber optic temperature probe positioned to read the temperature of said reaction vessel in said cavity (for controlling the microwave power delivered to said reaction vessel). 
     
     
         6 . A system according to  claim 4  that incorporates nitrogen pressure to transfer all reagents and to provide an inert environment during peptide synthesis. 
     
     
         7 . A system according to  claim 6  further comprising a nitrogen source in communication with said reaction vessel to bubble the contents of said reaction vessel for mixing during deprotection, coupling, and cleavage reactions. 
     
     
         8 . A system according to  claim 1  further comprising a processor for controlling every step in every SPPS cycle carried out in said system.