Oligopeptides with the sequences ala-pro-gly and gly-pro-gly as substrates or inhibitors for protocollagen proline hydroxylase.

Sequential oligopeptides prepared by condensation of peptides with the sequence Ala-Pro-Gly or Gly-Pro-Gly were examined as possible substrates or inhibitors for the synthesis of hydroxyproline by protocollagen proline hydroxylase. The tripeptide BOC-Ala-Pro-Gly-OMe (where BOC-represents 1-butoxycarboxyland Me represents methyl) was not hydroxylated, but oligopeptides ranging in size from BOC(Ala-Pro-Gly)lOMe to BOC(Ala-ProGly),OMe served as substrates for the synthesis of hydroxyproline. The results indicated that a peptide must contain a minimum of 4 to 6 amino acid residues in order to serve as a substrate, and they supported previous indications that a peptide of more than about 20 residues is required for optimal interaction with the enzyme. The oligopeptides H(Gly-Pro-Gly)20H and H(Gly-ProGly),OH were not substrates for the enzyme, but H(GlyPro-Gly)rOH was a competitive inhibitor for the hydroxylation of proline in the polymer (Gly-Pro-Pro), (synthesized as (Pro-Gly-Pro),). Comparison of H(Gly-Pro-Gly),OH with H(P~o)~~OH indicated that H(Gly-Pro-Gly),OH was a more effective inhibitor than the proline homopeptide with the same number of amino acid residues. A polymer with the permuted sequence Gly-Pro-Ala had a small inhibitory effect, and it also served as a substrate for the synthesis of hydroxyproline at a small but significant rate.