Chemical synthesis of membrane proteins by the removable backbone modification method

This protocol describes how to chemically synthesize membrane proteins through the installation of solubilizing removable backbone modification tags into hydrophobic transmembrane peptides. The implementation of the protocol is demonstrated by the chemical synthesis of phosphorylated M2 (M2-pSer64), a 97-aa proton channel protein from the influenza A virus. The synthesis of M2-pSer 64 at milligram scale takes ∼200 working hours (excluding the time for lyophilizations).