Segregated folding determinants for small disulfide-rich peptides

摘要

The preparation of small peptides with multiple disulfide bonds is accomplished by forming a prepropeptide with an N-terminal excised region separated from the cysteine-rich peptide by one or more cleavable amino acid residues. The excised region preferably consists of an N-terminal end providing a hydrophobic signal sequence domain having up to approximately 25 amino acids, and an intermediate central propeptide domain having a variable length of between about 5-50 amino acids. The N-terminal excised region serves as a folding template to direct the formation of specific disulfide bonds in the cysteine-rich peptide. The cysteine-rich peptide is cleaved by enzymes releasing the biologically active peptide.