Design considerations for pilot scale solid phase peptide synthesis reactors

Abstract

Large scale solid phase peptide synthesis can produce molar quantities of chains of specific amino acid sequences. Since the chains lengthen in a stepwise manner incomplete reactions cause impurities which decrease synthetic yield and pose significant purification problems. Therefore, solid phase peptide synthesis requires sequential heterogeneous reactions and extractions which must approach complete conversion and mass transfer. Laboratory methods for this process sequence have shown that a single vessel suitable for agitation and filtration is the most efficient means to ensure that solid material is not lost from step to step. The initial developmental approach of large scale peptide synthesis reactors has emphasized highly versatile automated systems which reflect reaction sequences used in laboratory scale synthesis. Present and future development of solid phase reactors is identifying physico-chemical parameters such as shear requirements, flow patterns, and reaction kinetic requirements important to the process. Subsequently, this information is used to allow alternate large scale reactor design for the system. This discussion gives examples of both developmental approaches with a consideration of the rheological, mass transfer, and kinetic problems inherent in the coupling and deblocking reactions and the intermediate extraction washes.