Synthesis of a series of analogous peptides using T-bags

To obtain a number of analogous peptides differing only in side chains in one or two positions, it may be convenient to perform the synthesis on resin confined to a number of porous bags (which are described as T-bags), so that when residues that are to be changed are coupled, a bag containing the peptidyl resin can be isolated from other bags and coupled to a different protected amino acid. At the completion of coupling, the bag may be returned to a bottle containing the other bags, and the synthesis continued. The principal and usefulness of this method was originally described by Houghton (1), who synthesized several hundred peptides at once in one step in order to explore the contribution of individual side chains in the specificity of antibody binding sites. The use of Fmoc chemistry and acid-labile resin means that peptides may be cleaved from the resin samples by individual reactions with TFA. If a method using tBoc chemistry is used as described by Houghton (1), then special apparatus to handle many individual reactions with HF to cleave the peptides from the resin at the end of synthesis is required.