The nature of protein has implications on the experimental design. Hydrophobic proteins such as membrane proteins can suffer from aggregation and poor solubility. A solution that could address these issues is to recruit first-generation removable backbone modification (RBM), which minimizes aggregation whilst allowing conjugation to a poly-arginine solubility tag (Table , Entry 21). The RBM is installed via a removable glycine auxiliary and thus has limited scope. A second-generation RBM was designed to be installed into all other amino acids, including the challenging Val-Ile junction, making this highly attractive for the synthesis of membrane proteins (Table , Entry 22; Figure ). The RBM tags have been employed in the synthesis of the mirror-image TIGIT membrane protein domain. In addition to RBMs, removable solubilizing tags could also be incorporated onto lysine side chains (Fmoc-Ddae-OH) or (Fmoc-Ddap-OH) using the 'helping-hand' strategies (Table , Entries 19-20). Whilst no Dproteins are currently reported using this method, these tags could possibly be installed onto commercially available D-amino acid building blocks. The lysine tags can also be employed to install click handles for templated chemical protein ligations. Figure : Second generation removable backbone moficiation. 4-methoxy-5nitrosalicylaldehyde is installed onto backbone nitrogen during Fmoc-SPPS, followed by assembly of peptide main chain and desired tag sequence. Reversible acetylation of phenol group controls TFA lability for tag removal.