Merrifield-type peptide synthesizer

In preparing these various libraries, extensive use is made of solid phase synthetic methods. These methods are all derived from the solid phase peptide synthesis (SPPS) method developed by Merrifield in 1963. When performing a large number of syntheses, it is preferable to perform the synthetic steps on a solid bead rather than completing the entire synthesis in the solution phase. The solid-phase technique makes byproduct removal and final compound purification easier. The organic chemistry literature contains a wealth of different types of solid-phase supports and novel linkers for attaching the synthetic substrate to the bead. 

Two decades later, Furka [24,86] introduced the production of solid-phase peptide libraries, forming these by extending Merrifield s procedure. Such peptide libraries were mainly used as an improved method of searching for new pharmaceutically applicable peptide derivatives. It was gradually realized, that such compounds have limited variability and that, in general, peptides are often at disadvantages when administered orally. Consequently, it was also realized that widely differing libraries of other types of chemical compounds can be formed by solid-phase multistep syntheses [87]. 

In most of the published Merrifield syntheses the peptides are bound to polystyrene by benzyl ester type of linkages, which in analogy to classical methods can be cleaved by HBr/acetic acid. Already in the incipience period of the methodology, however, trifluoroacetic acid saturated with hydrogen bromide was found more efficient, first, because of the increased acidity of the mixture which in addition does not cause proton catalyzed acetylation and, second, since trifluoroacetic acid is more lipophilic than the acetic one, it solvates much better both the polymer and the peptide to be released. 

In the present monograph, we have dealt with solid-phase peptide synthesis as one of the several types of organic syntheses that can be achieved using polymeric reagents. The extensive literature on this topic will not be discussed here since it has been reviewed by Erickson and Merrifield (1976). Only important references, which cover the progress of the work in this field, are given. The three important sources available which survey the annual progress in this field are ... 

An example of the first type is the nthesis of cystine peptides. Tri-Cys-Cys-Ala-0-CHj-( was synthesized on a Merrifield polymer. 

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