Tactics and Strategy in Peptide Synthesis

Abstract

Over and above the problems of activation, coupling, protection and removal of protecting groups there are some more general aspects of peptide synthesis which, in order to be treated in a systematic manner, need to be identified and defined. Thus, schemes for the combinationof various protecting groups have to be developed for syntheses in which certain blocking groups, e.g. those applied for the masking of the α-amino function, must be removed after coupling, while others are expected to stay intact throughout the chain building process. Considerations which govern the selection of protecting groups and coupling methods can be designated as tactics.A separate, although not independent, part of the plan of a synthesis of a large peptide is the general design of the synthetic scheme. Decisions such as the construction of a long chain from larger segments or from single residues, form the strategy of synthesis. A further category, the techniquesof peptide synthesis, encompasses methods of facilitation, the choice between synthesis carried out in solution and chain building in which the peptide is anchored to an insoluble support. Experimental devices which simplify the isolation of intermediates or dispense with their isolation will also be discussed among the varieties of techniques proposed for peptide synthesis. It seems to us, that for the sake of exact communication between peptide chemists, these concepts [1–3] have to be clearly distinguished and consistently described with appropriate terms.