Chemical modification of a pepsin inhibitor from the activation peptides of pepsinogen.

Abstract

The peptide comprising the first 16 amino acids of porcine pepsinogen, prepared from the activation mixture, has been modified by guanidination of its three lysine residues to form homoarginine residues. The modified peptide is a better pepsin inhibitor than is the native peptide; for 50% inhibition of the milk-clotting action of pepsin at pH 5.3, the molar ratio of peptide to pepsin required is 9 for the native inhibitor and only 2 for the guanidinated inhibitor. Stepwise removal by Edman degradation of the amino-terminal Leu-Fal-Homoarg residues from the guanidinated inhibitor decreased the activity slightly at the first step and markedly at the second and third steps. Thus, all of the amino-terminal sequence except the leucine residue is necessary for full activity.