teps: (1) protection; (2) coupling; (3) deprotection; (4) isolation; and (5) characterization of the intermediates. With large peptides composed of many amino acids, these steps can be both repetitive and time-consuming. Fortunately, various processes have been developed to make the procedures less difficult (2:249-263).
Most chemical syntheses employ either solid phase peptide synthesis (SPPS) or liquid phase peptide synthesis (LPPS) methods (5:3697). Solid phase peptide synthesis techniques were developed by Merrifield (1963). The researcher used SPPS to synthesize tetrapeptide L-leucyl-L-alanyl-glycyl-L-valine (1:147). The methods typically involve attaching amino acids to an insoluble polymeric support. Such supports may consist of resins or gels. Peptide derivatives remain attached to the support during washing. They are only separated from the support when chain building is complete (1:147).
Solid phase peptide synthesis, therefore, provides an easy way of separating peptide derivatives from starting materials, reagents, and by-products. The technique facilitates syntheses by making intermediate isolation through either extraction or crystallization methods unnecessary. Moreover, without the various problems associated with intermediate isolation, the entire process can be mechanized and automated.
Numerous instruments are currently available for automatic SPPS. Additionally, these devices may take various different approaches to any particular peptide synthesis (11:1249). However, regardless of the different individual reactions involved, the techniques generally provide "continuous analytical control of chain building (2:249-263)."
A second procedure used for the chemical synthesis of peptides employs liquid phase methods. As with SPPS, LPPS also facilitates the separation of intermediates. However, instead of using an insoluble polymeric support, liquid phase syntheses occur in solution. There a...