One of the most critical factors in the success of a solid phase synthesis is the choice of linker. The linker must be stable during synthesis then cleaved under conditions that do not damage the product. Ideally then the cleavage conditions should be both mild and selective. For this reason resin/linker systems such as 3 have been designed for cleavage by enzyme. 3 was synthesised using a variety of spacers and solid supports, starting from either soluble linker 1 or support bound aldehyde 2. Activation of the ethylthiolate group of 3 and subsequent displacement by primary and secondary alcohols gave 4 in good yield. Both enzymatic and acidic cleavage of alcohol from 4 was investigated. As the acid stability of 4 could be modulated depending on the nature of the spacer it was possible to induce cleavage under very mild acidic conditions. (Fig. 9898) The utility of 3 was demonstrated by coupling of Fmoc serine methyl ester through the side-chain hydroxyl functionality and subsequent elaboration to a pentapeptide (H-SAVSS-OMe). This approach could find application in the synthesis of cyclic peptides and peptides with modified C-termini.