Enzyme-labile protecting groups have emerged as a green alternative to conventional protecting groups. These groups introduce a further orthogonal dimension and eco-friendliness into protection schemes for the synthesis of complex polyfunctional organic molecules. S-Phacm, a Cys-protecting group, can be easily removed by the action of a covalently immobilized PGA enzyme under very mild conditions. Herein, the versatility and reliability of an eco-friendly combination of the immobilized PGA enzyme and the S-Phacm protecting group has been evaluated for the synthesis of diverse Cys-containing peptides.