Protective group on side functions

This way out also is the subject of numerous contributions in the literature reviewed [16, 33, 35]. The unique aim of all is the synthesis of spacers or handle molecules, inserted between the phenyl moieties of the cross-linked polystyrene thread and a reactive group, not only to attach protected amino acids suitable for peptide synthesis to the polymer, but to facihtate peptide cleavage without loss of protecting groups on side functions (see Fig. 16). 

Besides this fundamental reason one has to realize that the result of even a most accurate multistep synthesis on polymer can be questioned by the chemical reaction necessary to release the final product from its support. Parts of the target sequence can be destroyed and desired protecting groups on side functions may be cleaved. These facts furthermore multiply the possibility for contaminations. Therefore, the overall success of any Merrifield peptide synthesis is inherently related also to the quality of isolation and purification procedures (see for example [168]). 

It should be mentioned in this connection that the conditions of peptide total hydrolysis cannot be recommended to analyze quantitatively the load of a polymer support by amino acid derivatives. Depending on the natur of the amino acids and type of protecting groups on their side functions, the amino acids hydrolyzed in the presence of the support interplay with the macromolecular coil in an unmethodical manner and therefore are not recoverable in their accurate proportions. In general, it is very deUcate to wash those polar molecules completely out of a lipophilic polymer tracery. 

The method of liberation of the end product from its support depends, first, on the type of C-terminal anchor bond to the polymer and, second, on the question of whether the synthetic material has to be released fully protected, partially masked but with free carboxylic terminus, or entirely deprotected. These aspects are part of the strategic concept — as mentioned in the beginning — which have to be carefully considered before the Merrifield synthesis is initiated. The conditions of deprotection of the mobile temporary N-terminal protecting group and those to cleave masking groups from side functions of the desired peptide are interrelated with the detachment conditions projected to liberate the end product from its support. 

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