3. Fmoc/tBu SPPS Unlike the Merrifield approach (Figure 2) which utilizes a regime of graduated acidolysis to achieve selectivity in the removal of temporary and permanent protection, the Fmoc/tBu method (5) is based on an orthogonal protecting group strategy, using the base-labile N-Fmoc group for protection of the a-amino group and acid-labile side-chain protecting groups and resin 3. Fmoc/tBu SPPS Unlike the Merrifield approach (Figure 2) which utilizes a regime of graduated acidolysis to achieve selectivity in the removal of temporary and permanent protection, the Fmoc/tBu method (5) is based on an orthogonal protecting group strategy, using the base-labile N-Fmoc group for protection of the a-amino group and acid-labile side-chain protecting groups and resin linkage agents. Since removal of temporary and permanent protection is effected by completely different chemical mechanisms, side-chain protecting groups and linkage agents can be employed that are removed under considerably milder conditions than those used in the Merrifield method. In practice, t-butyl- and trityl-based side-chain protection and alkoxybenzylbased linkers are used as they can be removed with TFA. This reagent is an excellent solvent for peptides, can be used in standard glass laboratory glassware, and being volatile is readily removed by evaporation. Indeed, it is this convenience of the cleavage reaction and the ease with which the method