DESIGN AND SYNTHESIS OF A CONSENSUS SIGNAL SEQUENCE THAT INHIBITS PROTEIN TRANSLOCATION INTO ROUGH MICROSOMAL VESICLES

Most signal sequences vary considerably in length and primary sequence, but possess some common structural features. Analysis of known signal sequences led to the design of a 19-residue sequence that, although not a naturally-occurring signal, possesses the structural features that commonly occur in pre-proteins. This peptide was synthesized by solid-phase methods, and inhibits in a concentration-dependent manner, the processing in vitro of nascent pre-prolactin, pre-forms of pancreatic digestive enzymes and pre-placental lactogen. The peptide acts at the cytoplasmic surface of microsomal vesicles added to the protein translation system, preventing translocation of the nascent chains to the lumenal space of vesicles where signal peptidase normally cleaves to remove the signal from nascent pre-proteins.