Local conformations of peptides representing the entire sequence of bovine pancreatic trypsin inhibitor and their roles in folding.

The conformational properties of seven overlapping peptides, 9 to 16 residues long, that comprise the entire primary structure of bovine pancreatic trypsin inhibitor (BPTI) have been characterized by circular dichroism and 1H nuclear magnetic resonance. The peptides are largely disordered, although apparently with somewhat different average conformational propensities of the polypeptide backbone, similar to those indicated by methods to predict secondary structure. Reduced BPTI appears to be approximately the sum of the individual peptides. Several local interactions involving aromatic rings of side-chains interacting with groups nearby in the primary structure have been identified and verified by replacing the responsible side-chains. The roles of these interactions in folding of reduced BPTI could be determined, as the conformational and nuclear magnetic resonance properties of all the major disulphide intermediates are known. Two of these local interactions contribute to the folding process and to stability of the fully folded conformation, whereas the other two do not.