Inhibitors of procollagen N-protease. Synthetic peptides with sequences similar to the cleavage site in the pro.alpha.1 (I) chain

Abstract

A series of peptides was synthesized with amino acid sequences identical to the cleavage site at which the procollagen N-protease cleaves the N-terminal propeptide from the pro.alpha.l chain of type I procollagen. Peptides up to 11 residues in length did not serve as substrates for the enzyme, an observation consistent with the demonstration that the N-protease will not cleave denatured procollagen or dissociated pro.alpha. chains. Several of the peptides served as effective inhibitors of the cleavage of procollagen. Comparison of the inhibitor activities of peptides of varying lengths suggested that the L-phenylalanine found 3 residues to the left of the cleavage site was important for inhibitor activity. This was confirmed by synthesis of analogs of inhibitory peptides in which L-phenylalanine was replaced by D-phenylalanine, tyrosine, lysine, aspartic acid or glycine.