Synthesis of the pro-peptide of subtilisin BPN'

Subtilisin, a bacterial serine protease, is secreted as pre-pro-subtilisin. Previously, we demonstrated that the pro-peptide moiety of intact pro-subtilisin can guide the folding of inactive protein to active enzyme both in an intramolecular (6) and intermolecular manner (18). Herein is reported the total chemical synthesis of the pro-sequence (77 amino acids) of pre-pro-subtilisin BPN' carried out by solid phase methods. The structure was confirmed by both sequencing and amino acid analysis of the fragment peptides resulting from a V-8 protease digest. Preliminary studies indicate that the synthetic pro-peptide itself can renature denatured subtilisin BPN'. This study demonstrates a novel method for examining protein folding with the aid of exogenously added synthetic peptides.